iLib08 - Citavi Andreu, G.; Boccaccio, C.; Leguen, J. P.; Oleggini, M.

(1992): Ultraviolet light-induced immunomodulation: a possible new tool in organ transplantation. In: Annales de médecine interne, Jg. 143 Suppl 1, S. 52–56. Schlagwörter Adjuvants, Immunologic; Animals; Bloodradiation effects; Humans; Immunityradiation effects; Organ Transplantation; Ultraviolet Rays Böhm, M.; Luger, T. A. (2004): [Alpha-melanocyte-stimulating hormone. Its current significance for dermatology]. In: Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete, Jg. 55, H. 5, S. 436–445. Online verfügbar unter doi:10.1007/s00105-004-0729-0. Abstract Alpha-melanocyte-stimulating hormone (alpha-MSH) is a tridecapeptide that was originally characterized as a neuropeptide derived from the pituitary gland. alphaMSH is synthesized from pro-opiomelanocortin (POMC) by the action of specific prohormone convertases which cleave POMC into alpha-MSH, adrenocorticotropin and beta-endorphin. The various effects of alpha-MSH are mediated via melanocortin receptors. The skin as well as the majority of cutaneous cell types express POMC. Proinflammatory stimuli such as ultraviolet (UV) light induce POMC expression and alpha-MSH secretion. Receptors for alpha-MSH are not only expressed by melanocytes, where they mediate melanogenesis and proliferation, but also by virtually every cutaneous cell type. Accordingly, alpha-MSH elicits a plethora of biological actions in these cell types including immunomodulation, protection from oxidative stress and UV-induced apoptosis, modulation of secretory epithelial function and regulation of extracellular matrix composition. These actions may be exploited in future by using super potent and truncated MSH peptides for the treatment of various skin disorders including inflammatory dermatoses. Schlagwörter Adjuvants, Immunologicmetabolism; Dermatologymethods; Humans; Melanocytesmetabolism; Pro-Opiomelanocortinmetabolism; Skinmetabolismradiation effects; Skin Diseasesdrug therapy; Ultraviolet Rays; alpha-MSHmetabolismtherapeutic use Byrne, Scott N.; Ahmed, Jarin; Halliday, Gary M.: Ultraviolet B but not A radiation activates suppressor B cells in draining lymph nodes. In: Photochemistry and photobiology, Jg. 81, H. 6, S. 1366–1370. Online verfügbar unter doi:10.1562/2005-04-20-RA-495. Abstract Immunosuppressive doses of solar-simulated UV radiation activate lymph node B cells that can suppress primary immunity by inhibiting the function of dendritic cells. The aim of this study was to determine the waveband responsible for activation of these suppressor B cells. We exposed C57BL/6 mice to various doses of either UVA or UVB radiation and analyzed the number and activation state of lymph node antigen-presenting cells (APC). Immunosuppressive doses of UVB but not UVA activated B cells as assessed by major histocompatibility complex II (MHC II) expression and doubled their numbers in draining lymph nodes. Higher doses of UVA that were not immunosuppressive actually suppressed B cell activation. Our results show that UVA and UVB suppress systemic immunity via different mechanisms. Lymph node B cells are activated in response to immunosuppressive doses of UVB but not UVA. Thus, the activation state of lymph node APC appears to be important for UV immunomodulation. Schlagwörter Animals; B-Lymphocytescytologyimmunologyradiation effects; Dendritic Cellscytologyimmunologyradiation effects; Female; Immune Tolerance; Lymph Nodesimmunology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Ultraviolet Rays Cooper, Kevin D.; Baron, Elma D.; Matsui, Mary S. (2003): Implications of UV-induced inflammation and immunomodulation. In: Cutis; cutaneous medicine for the practitioner, Jg. 72, H. 3 Suppl, S. 11-5; discussion 16. Abstract Sunscreens are the most effective and widely available interventions for sun damage, other than sun avoidance or clothing. However, sun-screens vary widely in their ability to screen various UV wavelength components. Testing methods for sunscreens rely on UV-induced erythema to determine a sun protection factor

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(SPF), primarily a measure of UVB protection only. Determination of an immune protection factor (IPF) has been proposed as an alternative or adjunctive measure to SPF, and, indeed, recent studies show that the IPF can detect the added in vivo functionality of sunscreens--such as high levels of UVA protection--that the SPF cannot. Consensus on the definition of IPF, however, is required. Data are available on quantification of the IPF for restoring the afferent or induction arm of contact sensitivity, but other immune parameters also have been measured. A review of in vivo studies in humans, in which sunscreens are used to intervene in UV-induced modulation of immune response, cells, or cytokines, highlights the technical variables and statistical approaches that must be standardized in the context of an IPF for regulatory product claim purposes. Development of such IPF standards would allow the integration of both UVB and non-UVB solar wave-band effectreversals. In addition, it could be applied to integrate the effects of other ingredients with protective function (ie, antioxidants, retinoids, or other novel products) and spur the development of more advanced and complete protection products. Humans; Inflammationetiologyimmunologypathology; Skinimmunologyradiation effects; Sunscreening Agentspharmacology; Ultraviolet Raysadverse effects

Garssen, J.; van Loveren, H. (2001): Effects of ultraviolet exposure on the immune system. In: Critical reviews in immunology, Jg. 21, H. 4, S. 359–397. Abstract Depletion of stratospheric ozone and changes in lifestyle lead to an increased exposure to ultraviolet (UV) wavebands, especially in the UVB region (280-320 nm). Besides the beneficial effects of UV exposure, such as vitamin D production, cosmetic tanning, and adaptation to solar UV, UV exposure can also have adverse consequences on human health, notably sunburn, skin cancer, and ocular damage. Over the last two and a half decades it has become evident that especially UVB exposure and to a lesser extent UVA modulates specific as well as nonspecific immune responses. Several reports have shown that this immunomodulation plays at least a partial role in the induction of skin cancer. In addition, UVB exposure has been demonstrated to impair resistance to some infections. On the other hand, immunomodulation resulting from UVB exposure might be physiologically important in inhibiting responses to neoantigens in the skin induced by UV exposure. In the last 20 years UV has been used frequently as an experimental tool to unravel immune responses-especially immune responses initiated in the skin (i.e., photoimmunology). In this review, the major mechanisms responsible for UVinduced immunomodulation and its consequences are summarized. Schlagwörter Animals; Cytokinesimmunology; Humans; Immune Systemradiation effects; Photoreceptor Cellsimmunology; Ultraviolet Rays Hart, P. H.; Grimbaldeston, M. A.; Finlay-Jones, J. J.: Sunlight, immunosuppression and skin cancer: role of histamine and mast cells. In: Clinical and experimental pharmacology & physiology, Jg. 28, H. 1-2, S. 1–8. Abstract 1. The development into tumours of skin cells transformed by ultraviolet (UV) B radiation of wavelengths 290-320 nm is enhanced by the ability of UVB to suppress an immune response that would otherwise destroy them. Ultraviolet B-induced immunomodulation may be by multiple mechanisms, but generally manifests in an antigen-presenting cell defect and an altered cytokine environment in the draining lymph nodes. 2. Immune responses to microbial or self-antigens may be dysfunctional by similar mechanisms following UVB exposure. 3. Earliest-acting intermediates in the initiation of UVB-induced immunosuppression are the UVB absorbers (photoreceptors) of the skin, notably DNA resulting in immunoregulatory cytokine production, and trans-urocanic acid (UCA), which, upon isomerization to its cis isomer, signals downstream immunosuppressive events. 4. In mice, dermal mast cells are critical to UVB-induced systemic immunomodulation. In mice, there is a functional link as well as a linear relationship between the prevalence of histamine-staining dermal mast cells and the log of the dose of UVB required for 50% immunosuppression. Studies with histamine receptor antagonists support

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histamine as the main' product of mast cells involved. Histamine acts in large part via a prostanoid-dependent pathway. 5. Approximately 50% of humans and greater than 90% of patients with non-melanoma skin cancer are UVB susceptible for suppression of a contact hypersensitivity response. Neither cytokine polymorphisms nor UVB-induced levels of cis-UCA in irradiated skin have been linked to UVB susceptibility. Patients with basal cell carcinomas (BCC) have an increased dermal mast cell prevalence in non-sun-exposed buttock skin. We propose that mast cells function in humans, as in mice, by initiating immunosuppression and, thereby, allowing a permissive environment for BCC development. Animals; Carcinoma, Basal Cellimmunologymetabolism; Dermatitis, Contactimmunologymetabolism; Histamineimmunologymetabolismradiation effects; Humans; Immunosuppression; Mast Cellsimmunologymetabolismradiation effects; Mice; Neoplasms, Radiation-Inducedimmunologymetabolism; Skin Neoplasmsimmunologymetabolism; Ultraviolet Raysadverse effects

Hart, P. H.; Grimbaldeston, M. A.; Finlay-Jones, J. J.: Mast cells in UV-B-induced immunosuppression. In: Journal of photochemistry and photobiology. B, Biology, Jg. 55, H. 2-3, S. 81–87. Degranulating dermal mast cells in UV-B-irradiated skin have been implicated for Abstract many years in the mechanisms of irradiation erythema. There is now considerable evidence that dermal mast cells are important to the processes by which both UV-B radiation and cis-urocanic acid (cis-UCA) suppress immune responses to sensitizing antigens applied to non-irradiated/non-cis-UCA-exposed sites. Mast-celldepleted mice are resistant to the immunosuppressive effects of UV-B radiation and cis-UCA for 'systemic' immunomodulation. However, these mice gain responsiveness if the dorsal skin is reconstituted six weeks prior to irradiation or cisUCA administration at that site with cultured bone-marrow-derived mast cells from +/+ mice. The molecular triggers for initiating mast-cell degranulation are being actively sought. Evidence suggests that histamine, and not tumour necrosis factor alpha, is the major mast-cell product that signals altered immune responses to sensitizing antigens applied to non-irradiated, non-cis-UCA-exposed sites. Histamine may have multiple roles, but experiments with indomethacin administered to mice have shown that one process involves induction of prostanoid production. Schlagwörter Animals; Bone Marrow Cellscytology; Immunosuppression; Mast Cellsdrug effectsimmunologyradiation effects; Mice; Skindrug effectsimmunologyradiation effects; Ultraviolet Rays; Urocanic Acidpharmacology Hurks, H. M.; van der Molen, R. G.; Out-Luiting, C.; Vermeer, B. J.; Claas, F. H.; Mommaas, A. M. (1997): Differential effects of sunscreens on UVB-induced immunomodulation in humans. In: The Journal of investigative dermatology, Jg. 109, H. 6, S. 699–703. Online verfügbar unter doi:10.1111/15231747.ep12340652. Abstract Ultraviolet radiation has been shown to suppress the (skin) immune system both in animal species and in humans. Whether sunscreens can prevent immunosuppression is a matter of debate. This study investigated the protective capacity of a commercial sunscreen lotion in humans. Part of the right arm of healthy volunteers was exposed to erythemagenic ultraviolet B doses of 160 mJ per cm2 for four consecutive days. Before irradiation, sunscreen was applied either directly onto the skin or onto a piece of quartz fixed to the skin (to avoid penetration of the sunscreen in the epidermis where it cannot block the photoisomerization of trans-urocanic acid in cis-urocanic acid in the stratum corneum). The control group was irradiated without prior application of sunscreen. Four h after the last irradiation, epidermal sheets were obtained by the suction-blister method from both arms and epidermal cells were used as stimulator cells in the mixed epidermal cell lymphocyte reaction. Responses directed to epidermal cells derived from irradiated skin were expressed as percentages of responses directed to epidermal cells derived from the nonirradiated left arm. The mixed epidermal cell lymphocyte

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reaction responses in the control group were found to be significantly increased (205%). This enhancement of the mixed epidermal cell lymphocyte reaction responses was associated with an influx of CD36+DR+ macrophages in the irradiated skin. Application of the sunscreen, either onto a piece of quartz or directly onto the skin, prevented the increase of the mixed epidermal cell lymphocyte reaction responses and the influx of CD36+DR+ cells. In an earlier study, volunteers were exposed three times weekly to suberythemagenic doses of ultraviolet B over 4 wk, resulting in mixed epidermal cell lymphocyte reaction responses that were decreased to 20%. The same sunscreen was not able to prevent this suppression. These contradicting results indicate that the protective effect of sunscreens with respect to ultraviolet-induced immunomodulation is critically dependent on the choice of ultraviolet treatment. Humans; Lymphocytesdrug effectsradiation effects; Macrophagesdrug effectsradiation effectsultrastructure; Skindrug effectsimmunologyradiation effects; Sunscreening Agentspharmacology; Ultraviolet Raysadverse effects

(1988): Immunomodulation: UV radiation. In: Transplantation proceedings, Jg. 20, H. 1 Suppl 1, S. 302–308. Schlagwörter Animals; Graft Enhancement, Immunologic; Graft Rejectionradiation effects; Graft vs Host Diseaseprevention & control; Hematoporphyrinspharmacology; Isoantigensimmunology; Lymphocyte Depletion; Mice; T-Lymphocytes, Cytotoxicdrug effectsradiation effects; T-Lymphocytes, Regulatoryradiation effects; Ultraviolet Rays Luger, T. A.: Immunomodulation by UV light: role of neuropeptides. In: European journal of dermatology : EJD, Jg. 8, H. 3, S. 198–199. Schlagwörter Cells, Cultured; Humans; Immune Systemradiation effects; Neuropeptidesphysiology; Pro-Opiomelanocortinphysiology; Skinradiation effects; Ultraviolet Rays Malina, L. (2003): [Urocanic acid and its role in the photoimmunomodulation process]. In: Casopís lékar̆ů c̆eských, Jg. 142, H. 8, S. 470–473. Abstract Urocanic acid (UCA) is a metabolite of the amino acid histidine. It represents an important chromatophore in epidermis, which can absorb ultraviolet rays in UVB and UVA region and sequentially convert it from trans- to cis-isomer. Cis-isomer is not further degraded; it accumulates in the skin and is excreted with sweat and in shedding keratin scales. UCA has several important functions, the regulation of the homeostasis of the acidic cutaneous surface, the terminal differentiation of epidermal cells and namely the immunomodulatory role. As and immunomodulator UCA can suppress contact allergic reaction and the delayed hypersensitivity of the organism. It can affect reactions mediated by Th-lymphocytes, cytokine system, Langerhans cells, and by some neuropeptides. UCA is related to the development of non-pigmented skin tumors (basaliomas) and indirectly also to pigmented tumors. Cis-UCA can inhibit both the local and systemic resistance to infectious agents. In the immunomodulation some adductive compounds with another important cutaneous chromatophore DNA can participate. Schlagwörter Adjuvants, Immunologic; Animals; Humans; Immune Tolerancedrug effectsradiation effects; Skinimmunologyradiation effects; Ultraviolet Rays; Urocanic Acidimmunologypharmacology Norman, P. E.; Powell, J. T. (2005): Vitamin D, shedding light on the development of disease in peripheral arteries. In: Arteriosclerosis, thrombosis, and vascular biology, Jg. 25, H. 1, S. 39–46. Online verfügbar unter doi:10.1161/01.ATV.0000148450.56697.4a. Abstract Vitamin D is generally associated with calcium metabolism, especially in the context of uptake in the intestine and the formation and maintenance of bone. However, vitamin D influences a wide range of metabolic systems through both genomic and nongenomic pathways that have an impact on the properties of peripheral arteries.

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The genomic effects have wide importance for angiogenesis, elastogenesis, and immunomodulation; the nongenomic effects have mainly been observed in the presence of hypertension. Although some vitamin D is essential for cardiovascular health, excess may have detrimental effects, particularly on elastogenesis and inflammation of the arterial wall. Vitamin D is likely to have a role in the paradoxical association between arterial calcification and osteoporosis. This review explores the relationship between vitamin D and a range of physiological and pathological processes relevant to peripheral arteries. Animals; Humans; Peripheral Vascular Diseasesepidemiology; Vitamin Dphysiology

Norval, M. (2001): Effects of solar radiation on the human immune system. In: Journal of photochemistry and photobiology. B, Biology, Jg. 63, H. 1-3, S. 28–40. On UV irradiation of the skin, a complex cascade of immunological changes results, Abstract initiated by cutaneous chromophores and ending in suppression of some local and systemic immune responses. In this review, the stages in this process are outlined first, concentrating on the roles of DNA and urocanic acid as photoreceptors. Evidence indicating UV-induced immunomodulation of delayed hypersensitivity and resistance to infectious diseases in human subjects follows. Aspects of genetic susceptibility to the immunosuppressive effects of UV exposure and extrapolation of the data obtained in animal models to the human situation are included. Finally uncertain and unknown factors relating to the impact of UV on the human immune system are discussed. Schlagwörter Animals; Communicable Diseases; Humans; Hypersensitivity, Delayedimmunology; Immune Systemradiation effects; Immune Tolerance; Immunityradiation effects; Solar Activity; Ultraviolet Raysadverse effects Pamphilon, D. H.; Alnaqdy, A. A.; Wallington, T. B. (1991): Immunomodulation by ultraviolet light: clinical studies and biological effects. In: Immunology today, Jg. 12, H. 4, S. 119–123. Abstract The interest of immunologists in ultraviolet (UV) irradiation stems from observations made in vitro and in vivo. In vitro, UV irradiation inhibits mitogen and mixed lymphocyte culture (MLC) responses and in vivo, it can induce cutaneous anergy, apparently via suppressor cells and serum factors. At present much interest is focused on the possible use of UV irradiation to permit transfusion without allosensitization and transplantation without either rejection or graft-versus-host disease (GVHD). Here, Derwood Pamphilon and colleagues discuss the current uses and potential of UV irradiation in transfusion and transplantation and relate these to experimental evidence on its effects at the cellular level. Schlagwörter Animals; Antigen-Presenting Cellsradiation effects; Antigens, Surfaceradiation effects; Blood Plateletsimmunologyradiation effects; Blood Transfusion; Bone Marrowimmunologyradiation effects; Bone Marrow Transplantationadverse effects; Calciummetabolism; Cytokinessecretion; Dogs; Graft vs Host Diseaseprevention & control; Humans; Immune Systemradiation effects; Immune Toleranceradiation effects; Mice; Rats; Secretory Rateradiation effects; Transplantation Immunologyradiation effects; Ultraviolet Rays Roberts, J. E. (2000): Light and immunomodulation. In: Annals of the New York Academy of Sciences, Jg. 917, S. 435–445. Abstract The immune system is susceptible to a variety of stresses. Recent work in neuroimmunology has begun to define how mood alteration, stress, the seasons, and daily rhythms can have a profound effect on immune response through hormonal modifications. Central to these factors may be light through an eye-brain hormonal modulation. In adult primates, only visible light (400-700 nm) is received by the retina. This photic energy is then transduced and delivered to the visual cortex and, by an alternative pathway, to the suprachiasmatic nucleus (SCN), the hypothalamic region that directs circadian rhythm. Visible light exposure also modulates the pituitary and pineal glands, leading to neuroendocrine changes.

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Melatonin, norepinephrine, and acetylcholine decrease with light activation, whereas cortisol, serotonin, GABA, and dopamine levels increase. The synthesis of vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP), and neuropeptide Y (NPY) in rat SCN has been shown to be modified by light. These induced neuroendocrine changes can lead to alterations in mood and circadian rhythm as well as immune modulation. An alternative pathway for immune modulation by light is through the skin. Visible light (400-700 nm) can penetrate epidermal and dermal layers of the skin and may directly interact with circulating lymphocytes to modulate immune function. In contrast to visible light, in vivo exposure to UV-B (280-320 nm) and UV-A (320-400 nm) radiation can alter normal human immune function only by a skin-mediated response. It is therefore important, when reporting neuroendocrine immune findings, to control the intensity, timing and wavelength of ambient light. Adult; Humans; Immune Systemphysiology; Neuroimmunomodulation; Photic Stimulation

Sandyk, R. (1993): Multiple sclerosis: the role of puberty and the pineal gland in its pathogenesis. In: The International journal of neuroscience, Jg. 68, H. 3-4, S. 209–225. Abstract Epidemiological studies demonstrate that the incidence of multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. It has been suggested that the manifestation of MS is dependent upon having passed through the pubertal period. In the present communication, I propose that critical changes in pineal melatonin secretion, which occur in temporal relationship to the onset of puberty, are intimately related to the timing of onset of the clinical manifestations of MS. Specifically, it is suggested that the fall in melatonin secretion during the prepubertal period, which may disrupt pinealmediated immunomodulation, may stimulate either the reactivation of the infective agent or increase the susceptibility to infection during the pubertal period. Similarly, the rapid fall in melatonin secretion just prior to delivery may account for the frequent occurrence of relapse in MS patients during the postpartum period. In contrast, pregnancy, which is associated with high melatonin concentrations, is often accompanied by remission of symptoms. Thus, the presence of high melatonin levels may provide a protective effect, while a decline in melatonin secretion may increase the risk for the development and exacerbation of the disease. The melatonin hypothesis of MS may explain other epidemiological and clinical phenomena associated with the disease such as the low incidence of MS in the black African and American populations, the inverse correlation with sun light and geomagnetic field exposure, the occurrence of relapses in relation to seasonal changes and fluctuations in mood, and the association of MS with affective illness and malignant disease. Therapeutically, this hypothesis implies that application of bright light therapy or the use of other major synchronizers of circadian rhythms such as sleep deprivation or application of external weak magnetic fields may be beneficial in the treatment and/or prophylaxis of relapses in the disease. Schlagwörter Adolescent; Adult; African Continental Ancestry Group; Age Factors; Age of Onset; Endocrine System Diseasescomplicationsphysiopathology; Female; Humans; Immune Complex Diseasesetiologyphysiopathology; Immune Systemphysiopathology; Male; Melatoninsecretion; Middle Aged; Multiple Sclerosisetiologyphysiopathologytherapy; Phototherapy; Pineal Glandphysiopathology; Puberty Sleijffers, Annemarie; Garssen, Johan; Vos, Joseph G.; Loveren, Henk (2004): Ultraviolet light and resistance to infectious diseases. In: Journal of immunotoxicology, Jg. 1, H. 1, S. 3–14. Online verfügbar unter doi:10.1080/15476910490438333. Abstract Exposure to ultraviolet (UV) radiation, as in sunlight, can modulate immune responses in animals and humans. This immunomodulation can lead to positive health effects especially with respect to certain autoimmune diseases and allergies.

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However, UV-induced immunomodulation has also been shown to be deleterious. Experimental animal studies have revealed that UV exposure can impair the resistance to many infectious agents, such as bacteria, parasites, viruses, and fungi. Importantly, these effects are not restricted to skin-associated infections, but also concern systemic infections. UV radiation induces a multistep process, locally in the skin as well as systemically, that ultimately leads to immunosuppression. The first event is the absorption of "UV" photons by chromophores, or so-called photoreceptors, such as DNA and urocanic acid (UCA) in the upper cell layers of the skin. Upon absorption of UV radiation, trans-UCA isomerizes to the cis-isomer. Cis-UCA is likely the most important mediator of UV-induced immunosuppression, as this compound has been shown to modulate the induction of contact type hypersensitivity and delayed type hypersensitivity, allograft rejection, and the functions of monocytes and T-lymphocytes as well as natural killer cells. The real consequences of UV-induced immunomodulation on resistance to infectious diseases for humans are not fully known. Risk estimations have been performed through extrapolation of animal data, obtained from infection models, to the human situation. This estimation indicated that UV doses relevant to outdoor exposure can impair the human immune system sufficiently to have effects on resistance to infections, but also indicated that human data are necessary to further quantify and validate this risk estimation. Further information has been obtained from vaccination studies in human volunteers as ethical reasons prohibit studies with infectious agents. Studies in mice and human volunteers on the effects of prior UVB exposure on hepatitis B vaccination responses revealed suppressed cellular and humoral immune responses in mice but not in human volunteers. However, subgroups within the performed human volunteer study made by determination of cytokine polymorphisms or UVB-induced mediators, revealed that some individuals have suppressed hepatitis B vaccination responses after UVB exposure. Thus, it might be concluded that the human immune system can be affected by UVB exposure, and decreased resistance to infectious diseases can be expected after sun exposure.

Srinivasan, Venkataramanujan; Spence, D. Warren; Pandi-Perumal, Seithikurippu R.; Trakht, Ilya; Cardinali, Daniel P. (2008): Therapeutic actions of melatonin in cancer: possible mechanisms. In: Integrative cancer therapies, Jg. 7, H. 3, S. 189–203. Online verfügbar unter doi:10.1177/1534735408322846. Abstract Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep/wake cycle, as well as circadian rhythms generally, melatonin is involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and animal studies have now shown that melatonin also has important oncostatic properties. Both at physiological and pharmacological doses melatonin exerts growth inhibitory effects on breast cancer cell lines. In hepatomas, through its activation of MT1 and MT2 receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth of prostate tumors via activation of MT1 receptors thereby inducing translocation of the androgen receptor to the cytoplasm and inhibition of the effect of endogenous androgens. There is abundant evidence indicating that melatonin is involved in preventing tumor initiation, promotion, and progression. The anticarcinogenic effect of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic properties. Melatonin's oncostatic actions include the direct augmentation of natural killer (NK) cell activity, which increases immunosurveillance, as well as the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12, and interferon (IFN)-gamma. In addition to its direct oncostatic action, melatonin protects hematopoietic precursors from the toxic effect of anticancer chemotherapeutic drugs. Melatonin secretion is impaired in patients suffering from

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breast cancer, endometrial cancer, or colorectal cancer. The increased incidence of breast cancer and colorectal cancer seen in nurses and other night shift workers suggests a possible link between diminished secretion of melatonin and increased exposure to light during nighttime. The physiological surge of melatonin at night is thus considered a "natural restraint" on tumor initiation, promotion, and progression. Animals; Antineoplastic Agentspharmacology; Cytokinesdrug effectsmetabolism; Humans; Killer Cells, Naturaldrug effectsmetabolism; Melatoninmetabolismpharmacology; Neoplasmsdrug therapyphysiopathology; Receptor, Melatonin, MT1drug effectsmetabolism; Receptor, Melatonin, MT2drug effectsmetabolism

Suke, Sanvidhan G.; Kumar, Achint; Ahmed, Rafat S.; Chakraborti, Ayanabha; Tripathi, A. K.; Mediratta, P. K.; Banerjee, B. D. (2006): Protective effect of melatonin against propoxur-induced oxidative stress and suppression of humoral immune response in rats. In: Indian journal of experimental biology, Jg. 44, H. 4, S. 312–315. Abstract Effect of melatonin in attenuation of propoxur induced oxidative stress and suppression of humoral immune response was studied in rats. Oral administration of propoxur (10 mg/kg) increased lipid peroxidation in serum after 28 days treatment. Superoxide dismutase, catalase and glutathione were also altered following propoxur exposure. In addition propoxur exposure markedly suppressed humoral immune response as assessed by antibody titre and plaque forming cell assay. Simultaneous treatment with melatonin (5 mg/kg, ip) markedly attenuated the effect of propoxur on (a) lipid peroxidation, (b) oxidative stress parameters and (c) immunotoxicity. Results have been discussed in the light of possible immunopotentiating and antioxidant effects of melatonin to understand the influence of oxidative stress on propoxur induced immunomodulation. Schlagwörter Animals; Antibody Formationdrug effectsimmunology; Antioxidantsmetabolism; Immunosuppressive Agentspharmacology; Male; Malondialdehydeblood; Melatoninpharmacology; Oxidative Stressdrug effects; Propoxurantagonists & inhibitorspharmacology; Rats; Rats, Wistar Tran, T. Thanh-Nga; Schulman, Joshua; Fisher, David E. (2008): UV and pigmentation: molecular mechanisms and social controversies. In: Pigment cell & melanoma research, Jg. 21, H. 5, S. 509–516. Online verfügbar unter doi:10.1111/j.1755-148X.2008.00498.x. Ultraviolet radiation (UVR) is an essential risk factor for the development of Abstract premalignant skin lesions as well as of melanoma and non-melanoma skin cancer. UVR exerts many effects on the skin, including tanning, carcinogenesis, immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in the maintenance of healthy bones as well as other purported beneficial effects, amongst which is the potential for reducing risk of malignancy--though oral supplementation is fully capable of maintaining systemic levels. The known medical harm from UV exposure relates primarily to cancer of the skin--the most common organ in man to be affected by cancer. In this review, we summarize the knowledge about the ultraviolet (UV) response in regards to inflammation, immunosuppression, carcinogenesis and the tanning response. We also discuss vit D and UV, as well as public health implications of tanning behavior and commercial interests related to the promotion of UV exposure. As the most ubiquitous human carcinogen, UVR exposure represents both a challenge and enormous opportunity in the realm of skin cancer prevention. Schlagwörter Humans; Immune Systemradiation effects; Lightadverse effects; Risk Factors; Skinmetabolismpathologyradiation effects; Skin Neoplasmsetiologypathologyphysiopathology; Skin Pigmentationphysiologyradiation effects; Ultraviolet Raysadverse effects; Vitamin Dmetabolism Wintzen, M.; Yaar, M.; Burbach, J. P.; Gilchrest, B. A. (1996): Proopiomelanocortin gene product regulation in

iLib08 - Citavi keratinocytes. In: The Journal of investigative dermatology, Jg. 106, H. 4, S. 673–678. Abstract Proopiomelanocortin (POMC) is the precursor for adrenocorticotropic hormone, melanocyte-stimulating hormones, beta-lipotropic hormone (beta LPH), and beta endorphin. These peptides can function as neurotransmitters, modulate immune responses, and affect melanogenesis. We investigated POMC expression and protein processing in normal human keratinocytes. On Northern blot analysis, the baseline expression of the 1.2-kb POMC transcript was upregulated by ultraviolet radiation (UVR) or by stimulation with interleukin-1 alpha (IL-1 alpha) or phorbol 12tetradecanoate 13-acetate (TPA). On Western blot analysis, POMC, beta LPH, and beta-endorphin were detected in cell extracts under baseline conditions. beta LPH level increased substantially after UVR, IL-1 alpha, or TPA. Within 36 h after TPA stimulation, beta-endorphin became undetectable in cell extracts, coinciding with an increase of beta-endorphin-immunoreactive protein in the culture medium. Our data establish that keratinocytes synthesize POMC protein as well as its derivatives beta LPH and beta-endorphin, and that this process is modulated by TPA, IL-1A, and UVR. beta LPH and beta-endorphin of keratinocyte origin may thus be involved in melanogenesis and/or immunomodulation in the skin after sun exposure, and their release into the circulation may also have systemic effects. Schlagwörter Cells, Cultured; Gene Expression Regulation; Humans; Interleukin-1pharmacology; Keratinocytesdrug effectsmetabolismradiation effects; ProOpiomelanocortinanalysisgenetics; RNA, Messengeranalysis; Tetradecanoylphorbol Acetatepharmacology; Ultraviolet Rays; betaEndorphinanalysis