ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease, the cause is not yet clear. Pathological manifestations are abnormal repair changes resulting from sustained lung injury. Macrophages have been identified as playing a key role in IPF pathogenesis. In different local microenvironments, macrophages can exhibit either classically activated (M1) or alternately activated (M2) phenotypes. M1 plays a key role in promoting inflammatory response and is involved in the process of causing alveolar tissue injury. M2 is involved in wound healing and stopping lung inflammation. Previous studies have shown that activation of 5-hydroxytryptamine (5-HT) signaling is enhanced in pulmonary fibrosis and that 5-HT receptors play an important role in the observed pro-fibrotic effects. As a multifunctional signaling molecule, 5-HT is closely related to lung macrophage polarization, early lung tissue injury, abnormal proliferation and repair, and late extracellular matrix (ECM) deposition. This article reviewed the role of 5-HT and M2 macrophages in the pathogenesis of IPF and the possible regulatory mechanism of 5-HT, in order to provide a reference for further research.
Subject(s)
Humans , Serotonin , Macrophages , Lung Diseases, Interstitial/pathology , Lung/pathology , Idiopathic Pulmonary Fibrosis , FibrosisABSTRACT
Objective:To study the mechanism of interleukin-10(IL-10)inhibiting the function of dendritic cells(DCs).Meth-ods:Cultured C57BL/6 mouse bone marrow-derived DCs were divided into 5 groups:control group,LPS stimulated group,IL-10 treated group,IL-10+Rapamycin treated group and Rapamycin treated group .The regulatory mechanism of IL-10 on dendritic cells were evalua-ted from DCs function ,Flow cytometry was used to analyse the expression of DCs surface co-stimulator CD80 ,CD40 expression ,the abil-ity of uptaking antigen and stimulating T cell to proliferate;ELISA was used to detect the cytokines IL-6 and TNF-α.Western blot was used to analyse the autophagy related protein LC3.Compared the differences between the groups.Results:(1)Compared to LPS stimu-lated group,IL-10 treated group,DCs surface co-stimulator CD40,CD80 were decreased,IL-6 and TNF-αsecretion level and the ability to stimulate T cell to proliferate were decreased ,the ability to capture OVA antigen was increased .Compared to IL-10 treated group ,the DCs surface co-stimulator CD80 was decreased ( P<0.05 ) ,IL-6 and TNF-αsecretion level and the ability to stimulate T cell to prolifer-ate were increased(P<0.0001)in IL-10+rapamycin treated group.In addition,autophagy related proteins LC3Ⅱ/LC3Ⅰwas decreased in IL-10 treated group.Conclusion:IL-10 may regulate functions of DCs through inhibiting the autophagy of DCs .