Suppression of inflammation in rat autoimmune myocarditis by S100A8/A9 through modulation of the proinflammatory cytokine network

Open Access
Publisher Website
Google Scholar
Abstract
Aims S100A8/A9 is expressed in activated monocytes/macrophages and assumed to be heavily involved in the pathogenesis of acute inflammation. Although several studies have asserted that S100A8/A9 has a proinflammatory function, the exact biological function of S100A8/A9 is yet to be described. We examined the anti‐inflammatory effects of S100A8/A9 on experimental autoimmune myocarditis (EAM) in rats. Methods and results Experimental autoimmune myocarditis was induced in Lewis rats by immunization with porcine cardiac myosin. The recombinant (R‐) S100A8/A9 was injected intraperitoneally into EAM rats. R‐S100A8/A9 attenuated the severity of myocarditis, as evidenced by echocardiographic and histological findings. In addition, we found that not only the mRNA expression of proinflammatory cytokines [interleukin (IL)‐1β, IL‐6, and tumour necrosis factor (TNF)‐α] in the myocardium, but also their serum concentrations were suppressed in EAM rats treated with R‐S100A8/A9. Nuclear factor‐kappa B expression in inflammatory cells was also suppressed in the treated rats. To elucidate the mechanistic function of S100A8/A9 on proinflammatory cytokines in vivo, we used an ELISA on the supernatant of homogenized heart tissue treated with R‐S100A8/A9. The findings revealed high‐affinity binding of R‐S100A8/A9 with IL‐1β, IL‐6, and TNF‐α in the myocardium, suggesting the trapping of proinflammatory cytokines by R‐S100A8/A9. Conclusion S100A8/A9 attenuates EAM through modulation of the proinflammatory cytokine network.

This publication has 31 references indexed in Scilit: