Mouse AIM/CD5L/Spα ELISA kit

Apoptosis inhibitor of macrophage (AIM, encoded by cd5l) is a multi-functional circulating protein that has a beneficial role in the regulation of a broad range of diseases, some of which are ameliorated by AIM administration in mice. In blood, AIM is stabilized by association with IgM pentamers and maintains its high circulating levels. The mechanism regulating the excessive accumulation of blood AIM remains unknown, although it is important, since a constitutive increase in AIM levels promotes chronic inflammation. Here we found a physiological AIM-cleavage process that induces destabilization of AIM and its excretion in urine. In blood, IgM-free AIM appeared to be cleaved and reduced in size approximately 10 kDa. Cleaved AIM was unable to bind to IgM and was selectively filtered by the glomerulus, thereby excreted in urine. Amino acid substitution at the cleavage site resulted in no renal excretion of AIM. Interestingly, cleaved AIM retained a comparable potency with full-length AIM in facilitating the clearance of dead cell debris in injured kidney, which is a key response in the recovery of acute kidney injury. Identification of AIM-cleavage and resulting functional modification could be the basis for designing safe and efficient AIM therapy for various diseases.

Objective Obesity-induced inflammation in white adipose tissue, characterized by increased macrophage infiltration and associated with macrophage population shift from anti-inflammatory M2 to proinflammatory M1 macrophages, largely contributes to obesity-induced insulin resistance and influences type 2 diabetes mellitus pathogenesis. GSK3 (glycogen synthase kinase 3), a serine/threonine kinase, has been reported to participate in various cellular processes. We sought to examine the potential mechanism by which GSK3, a serine/threonine kinase implicated in various cellular processes, modulates obesity-induced visceral adipose tissue (VAT) inflammation. Approach and Results Male C57BL/6J mice were fed a high-fat diet for 10 weeks while being treated with vehicle control or GSK3 inhibitors SB216763 or CHIR99021. RNA-sequencing results using VAT demonstrated that GSK3 inhibitor treatment reversed obesity-specific expression of genes associated with inflammation. Consistently, GSK3 inhibition reduced obesity-induced VAT inflammation as characterized by decreased proinflammatory M1 macrophages but increased anti-inflammatory M2 macrophages in the VAT and reduced circulatory inflammatory monocytes. These anti-inflammatory effects of GSK3 inhibition were found to be driven, at least in part, by inhibiting production of apoptosis inhibitor of macrophage in macrophages via inactivating STAT3 to reduce free fatty acid and chemokine level produced from VAT to suppress the migration/chemotaxis of macrophages and monocytes. Conclusions Our findings suggest that GSK3 may act as an important regulator of obesity-induced inflammation and characterize the novel role of GSK3 in shifting macrophage polarization and reinforce its therapeutic potential for obesity-induced inflammation and its associated diabetes mellitus.