title: The role of all-trans retinoic acid in bleomycin-induced pulmonary fibrosis in mice.
abstract: Much evidence suggests that immune imbalance in the lung plays a crucial role in the development of pulmonary fibrosis. Recently, all-trans retinoic acid (ATRA) shifting the regulatory T/T-helper 17 (Treg/Th17) profile had been proven in some diseases. However, to date, the effect of ARTA of pulmonary fibrosis has not been examined from this aspect. The objective of this study was to study the effect of ATRA on bleomycin-induced pulmonary fibrosis in mice and its possible mechanism. Pulmonary fibrosis was induced in C57BL/6 male mice by intratracheal instillation of bleomycin (5 mg.kg(-1)), which were randomly divided into control, bleomycin, and ATRA groups. Five mice in each group were sacrificed on day 28 after intratracheal instillation. Hemotoxylin and eosin (H&E) and Masson staining were used for pathological examination, and hydroxyproline in lung tissue was measured. Interleukin (IL)-17A protein expression was observed in lung with immunohistochemistry. The expression of IL-17A, IL-10, IL-6, and transforming growth factor (TGF)-β mRNAs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Th17 and Treg expression in spleen lymphocytes were measured by flow cytometry. H&E and masson staining and expression of hydroxyproline showed that ATRA significantly alleviated lung fibrosis than in the bleomycin group. The expression of IL-17A, IL-10, IL-6, and TGF-β mRNAs were higher in the bleomycin group than in the normal group. ATRA can decrease these cytokines except for IL-10. CD4+CD25+ Treg cell ratio in the bleomycin group was significantly lower than normal, but CD4+IL-17+ T cells was higher; ARTA reversed this kind of expression. ATRA may ease the bleomycin-induced pulmonary fibrosis by inhibiting the expression of IL-6 and TGF-β, shifting the Treg/Th17 ratio and reducing the secretion of IL-17A.
authors.affiliation: Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University, School of Pharmacy, Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Dong
authors.forename: Wenlin
authors.initials: W
authors.lastname: Tai
authors.forename: Yanni
authors.initials: Y
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Li
authors.forename: Yanling
authors.initials: Y
authors.lastname: Chai
authors.forename: Hong
authors.initials: H
authors.lastname: Zhong
authors.forename: Hua
authors.initials: H
authors.lastname: Zou
authors.forename: Dianhua
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000473:pathology; D058504:Th17 Cells / Q000187:drug effects / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D007378:Interleukins; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D014212:Tretinoin; D006909:Hydroxyproline