Activation of protease-activated receptor-2 is associated with increased expression of inflammatory factors in the adipose tissues of obese mice

Abstract

Previous studies have indicated that mast cells are critical for the pathogenesis of inflammatory diseases. Proteases released from mast cells have been reported to stimulate protease-activated receptors (PAR), which induces microleakage and widespread inflammation. In order to investigate the pro-inflammatory effect of PAR-2 activation on adipose inflammation in obese mice, the varying distributions of macrophages and PAR-2 in adipose tissue samples were compared between C57BL/6J (C57) and obese mice [B6(D)-Leprdb/J, BKS(D)Leprdb/J and B6.V-Lepob/J (ob/ob)] using immunohistochemical staining. Murine primary adipocytes and bone marrow-derived macrophages (BMDMs) were used and the alterations in expression levels of inflammatory factors, induced by PAR-2 activation, were detected by reverse transcription-quantitative polymerase chain reaction and ELISA. In addition, the migratory capacity of primary BMDMs and the macrophage cell line, RAW264.7 were evaluated by co-culture with primary adipocytes. The current study demonstrated a larger number of macrophages in the adipose tissues of obese mice compared with C57 mice. Furthermore, PAR-2 expression was detected in various adipose tissues of mice and the protein expression levels of PAR-2 were observed to be significantly higher in the total adipose tissues of ob/ob mice when compared with the C57 mice. The expression levels of inflammatory factors were increased in adipocytes and macrophages, and enhanced migratory ability was observed in macrophages pretreated with PAR-2 agonists. The data of the current study suggests that PAR-2 is involved in the process of obesity-associated chronic low-grade systemic inflammation, which indicates that the PAR-2 signaling pathway may be a potential target for the treatment of obesity and its associated diseases.