The role of all-transretinoic 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.

All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats

“…It has been reported that ATRA might ease bleomycin-induced pulmonary fibrosis via inhibition expressions of interleukin (IL)-6 and transforming growth factor (TGF)-b (Dong et al, 2012). Moreover, amelioration of EF was observed after inhibiting IL family and TGF family member expression (Yan et al, 2013;Zhang et al, 2013).…”

“…All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A that has a wide range of biological activities; it affects cell differentiation, proliferation, embryogenesis, inflammation and apoptosis (Dong et al, 2012;Datta and Lianos, 1999). It has been reported that ATRA might ease bleomycin-induced pulmonary fibrosis via inhibition expressions of interleukin (IL)-6 and transforming growth factor (TGF)-b (Dong et al, 2012).…”

siRNA-Act1 Inhibits the Function of IL-17 on Lung Fibroblasts via the NF-κB Pathway

“…Our previous study [5 ]and other studies [6,7,8]have demonstrated a possible contribution for IL-17A in the development of pulmonary fibrosis.…”

Association of all-trans retinoic acid treatment with the renin-angiotensin aldosterone system expression in glomerulosclerosis rats

“…4 Retinoic acid, as an active metabolite of vitamin A, includes all-trans retinoic acid (ATRA), 13-cis retinoic acid and 9-cis retinoic acid, and exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. 5 ATRA, as an important subgroup of retinoic acid, is a promising therapeutic agent for many diseases, such as acute promyelocytic leukemia, 6 pulmonary fibrosis, 7 renal interstitial fibrosis, 8 etc. In our previous study, we found that ATRA could achieve a similar effect to a RAAS inhibitor (benazepril) to prevent the progression of GS lesions in GS rats.…”