The Mechanisms of Resistin-Like Molecule--Mediated Airway Inflammation in Chronic Obstructive Pulmonary Disease via Autophagy

Background: The role of irreversible airway inflammatory damage in chronic obstructive pulmonary disease (COPD) progression is evident. Autophagy is an essential process in the cellular material metabolic cycle, and a family of resistant vegetative molecules may be involved in the COPD autophagic process. In this study, we investigated the mechanism of resistin-like molecule beta (RELM beta) in COPD smoking-induced autophagy. Methods: Firstly, the expression differences of RELM beta and autophagy markers between COPD and control groups were analyzed in the Gene Expression Omnibus (GEO) datasets and clinical specimens. Secondly, in vitro and in vivo experiments were conducted using immunoblotting, immunofluorescence, immunohistochemistry, and other methods to investigate the mechanism by which RELM beta promotes airway inflammation through autophagy in a cigarette smoke extract-induced 16HBE cell inflammation model and a cigarette smoke-induced COPD-like mouse model. In addition, immunoprecipitation was used to analyze the binding of RELM beta to the membrane protein TLR4. Results: The expression of RELM beta and autophagy genes p62 and LC3B in lung tissue of COPD patients was significantly increased. RELM beta can mediate the activation of autophagy in 16HBE cells, and through autophagy, it increases the expression of inflammatory cytokines in a cigarette smoke extract-induced 16HBE cell inflammation model. RELM beta promotes cigarette smoke-induced COPD-like mouse airway inflammation through autophagy, and RELM beta can mediate signal transduction through the cell membrane receptor TLR4. Conclusion: The RELM beta binds to TLR4 to encourage signal transduction and that RELM beta can promote inflammation in smoky COPD lungs through autophagy.