Respiratory Physiology & Neurobiology 266 (2019) 9-17 Contents lists available at ScienceDirect, Respiratory Physiology & Neurobiology journal homepage: www sisevier.com/locate/resphysiol Cigarette smoke exposure combined with lipopolysaccharides induced pulmonary fibrosis in mice Lijuan Fang", Qingmei Cheng’, Feiyan Zhao’, Haipeng Cheng’, Yongyu Luo”, Xingwen Bao", ‘Yanghang Li’, Xinyue Liang’, Yanhong Huang’, Jianping Xu’, Jianzhong Han’, Yiting Tang’, Siyuan Tang’, Wei Liu’, Ziqiang Luo’, DanDan Feng’ Doerr sbi, Mong Sel of Medene, Cel Sou desi, Cara, ar, Cae Mtoe ose Schoo Cote! Sul Uesk, Caan, Chine ARTICLE INFO ApsTRACT epee ‘Gigererte smoke (C5) saws factor for pulmonary Abeoas and lpopalysacehardes (LPS) ae assotated with Fmewty vse ‘umn occupational lang diseases however, their combined role in pulmonary Abross emai unkown ‘lara sake “Therefore, we ivestigated whether CS combined with LPS induces pulmosary fuss in mie. CSTBL/G mice Lpepetssearte ‘were exposed to CS of not airfor 2] 9 day, followed by LPS or saline instil on day 14 21, and 28 ‘Tang faetion was tested, and lung esues were harvested fr histlogieal and molecular analyses. Conipaeed to ‘he contol, CS and 125 goups, the CS + LPS group showed reuced body weight ae survival eae increased respiratory resintnes, decreed ling compliance, marked alveolar sructre destiction, and bate Isin formation, Ling tissues showed a considerable increase in L-, TNF-a, IL, «SMA, and TGR levels and cllagen content. ur esls indicate tat egaette eke expos elloted by LS n mie ndaces plenary fibrosis with pathophysiology consistent wie that of human pulmonary bros 1. Introduction Pulmonary flbrosis isa chronic, progressive, and ireversible lung restleted disease. Its the most common outcome of intetstital lung, ‘disease (Lit otal, 2016), which is characterized by alveolar epithelial cell damage and Iyperplasl, accumulation of inflammatory eels Dbroblast hyperplasia, extracellular matrix deposicen, and sear forma Hon (Moore and Hogaboam, 2008). ‘The aetlology of pulmonary fbross is complex, and Its beleved to be caused by genetic and various environmental factors suchas tobacco ‘stoke, meta, drugs, and contact wht Infetfous substances (hy & 3, 2014; Raghu et al, 2011; Sekman and Pardo, 2074). Its well known thar cigarette smoking induces chroale obstructive pulmonary disease (COPD), and In some heavy smokers, COPD disease manliests as both ‘pulmonary emphysema (upper lobe ofthe lung) and pulmonary fibrosis (ower lobe of the lang) (Cottn et al, 2005; Grubstein et al, 2005). ‘Smoking Is also belleved to be a high-risk factor for pulmonary Tors, ‘and smoking-induced pulmonary epidelil cell injury may persist for several years even after quitting smoking (Baumgartner et al, 1997), Such epithelial cell damage plays a Key tole in the activation of brogenesis, thereby contributing 1 the pathogenesis of pulmonary "Corresponding author ‘Bal adres: fnJandangies.c0.c0 . Feng. Intps//dobeng/10.2016/.2e59.2019.04010 ‘Abrosls. In vivo studles have shown that nicotine rectly affects the Fone homeostass of ung epltelial cells and provokes an inflamamatory Fesponse that contributes to cellar damage (Vloomns et al, 29075 ease et al, 2012). Lipopolysaccharides (LPS) are important cell wall components in fram-negative bacteria. LPS are ubigultous In he environment and associated with many human occupational lung diseases, most of which are associated with organle dust exposure (Thor, 2001). LPS promote the activation and aggregation of inflammatory cells and the produc- tion and release of other inflammatory mediators, resulting in diffuse Jung tissue damage (Maat eal, 2008; Sebal et al, 2009), IPS activate the mononuclear macrophage system to produce a several fbrogente cytokines such as transforming growth factor heta 1 (TGF-BL), whieh act on pulmonary fibroblasts via dferent direct ot Indirect pathways (Olman et al, 2004), Following this LPS-induced damage, the Hbroblasts induce chemotanis and activate pulmonary macrophages through inflammatory factorssuct as interleukin (I-6), {dus partilpating Inthe lung fibrosis process with other ces (V anche bp aly 19954 Seld etal, 2007) i fac, it fas been confirmed that LPS Alrectly activate Rbroblasts and promote eollagen synthesis and secre tion, eventually causing diffuse interstitial pulmonary fibross (He otal. Received 20 December 2018; Received in revised form 31 March 2019; Accepted 2) April 2019 Availabe online 22 April 2019 15699048/ © 2019 Elsevier LY. Al rights reserved1 roy 2009), Furthermore, rapid pulmonary fibrosis eould be induced by acute ung injury via the LPS tre: hit regimen (Let al, 2008; Heo a 2010) Icis known diat LPS are associated with many occupational lung 119-188 Nn se? tors phos bo eter, Rubin, Chang, AY. Penne. BP, Fak, 3. Oster 5. Fs, Recep. Pk. 1998, Palmas ages duced candied use bls Teter rst) and reiton n normal mieten ert pete fees atime Oncol 25, 212-208 pr Oeoty 10 10167 B14) Meo Bi Hogabum, CM, 2008, Mure mela ulnonary ess Am hs tC Pi 24 es La ge tree Moura, M4, Alinls, V., 2011. Modeling pulmooary fbrosts with bleomycin. Car. ‘Obi. Pi, Me 17, 366-61 oss 10.1097 ac sor seas, olnan SA, White RE Wate, L8, Snmote, WL, Benvense, 2,5. Pag, ‘Mats Mu 2004, Plntary eas ld on pets Wi aI ry ts Mbt pert hough IL? et nde IL expresion Iumuneh 172, 698-2677. r/o 40 Suanol 17242688 Paks HS. Kn, SR, ee, .c, 2000 pact of ove se on lung Sess, 7 Reins 2738 Mga an NOTUIA Tate Nee ae ‘Peonyiate and presi Aw © Aca Se 686, 12-29 so ie inirniavisaceaotoviae agh, 6, Cllr, HR. Ep, 1, Mabe, F., Bet 2 Be0on, KX, Clty, 1 Cord, J. Faber, WN, Lay, A, gnc, Da, 11 An ell ATSIERS? ‘Aston opi pay i dee hd ese gto ties eam soy oso fhm, L, Adee, LM, 2006. Crkatnestess an redox eubton hing amin om fe Rep 99 219-98 hp Hor ote, SN Howl, SEM, Wate, WAH, BROW, DAL, Lamb, Ramige EA (Donalsn, ke, 19%. novel el fr human era em ease: pte tren mg rons nents ato 17%, 90-016 Sse ono Tae pam711900013 Rooms, GA, Vananoung, Vv. Dragon, A, Koo, Weslest, 2002 ees fica oust and reper) ep, 2. Submits Ce Po Seta Hs en Ae, M, Sa, Aowef,Ghanem Boughnam S290. Protective ete of resveniel mentees iced eae pane repens a Ah ‘Tone 6-34, h/day 10.1007 sono 65 048 0 Seu E Deis, 6, Onecare, Os, Henne, Sea, "as 007. TA canes TGF bt geal a hepate oss Na ed 13, 1334-153, Ms oto /0.108 ames Sedan, ard, A, 2014, Reval the puboyeic and tng elated mechaisas of the ease lop palonay Neos. an gral mol i, J. Rep Ct soning et 3 EOL- 73 he ang orca at Engelhardt, 1, Lu, X, White, ES, Thasnickal 13040. Targeted nary of type tok eit as nce pulmonary Rest. A. 2 Rep 18), 24-268 hey doo oot rem 200810161500 ‘Thannical, V4, Fanbur, BL, 2000, Reactive oxygen species in cell signaling, Am. J Phil Lang all Mol, Phys 279, LANE bem ps Hse TES ing.2000279.04105, “thor, 200 The isrmstny respons im humane afer ih bein a reve am. Res 0, 25-261 ps ior 101077 son nierreh sister, A 1%. Human ing bs nay nce ator sph Pret by Ls seated manors Am Respir Cell Mol Bl 5, 490-466 Branton. agembte-8979077