CTRP3 Prevents Macrophage Activation

Abstract

Sepsis is a life‐threatening medical emergency that is caused by the body’s extreme response to an infection. The initial infection results in an overproduction of cytokines which recruits additional immune cells. Adipose tissue is an active endocrine organ which secrets several anti‐inflammatory mediators, collectively called adipokines which could contribute to the control of the body’s response to a septic event. Our previous work has identified that the circulating levels of the anti‐inflammatory adipokine called C1q TNF Related Protein 3 (CTRP3) is significantly reduced in response to sepsis. We have also demonstrated that CTRP3 binds directly to circulating macrophages. Therefore, the purpose of this project was to examine the potential anti‐inflammatory effects of CTRP3 on macrophages.METHODSThioglycolate‐induced peritoneal macrophages were isolated from CTRP3 overexpressing transgenic (Tg) and wild‐type (WT) mice. The isolated macrophages were then treated with lipopolysaccharides (LPS). Morphological changes were analyzed via bright‐field microscopy and the transcription levels of the inflammatory cytokines tumor necrosis factor alpha (TNF) and interleukin‐6 (IL6) were measured by Real‐Time PCR.RESULTSMorphological qualitative analysis indicated that LPS reduced macrophage adhesion and the effect was more pronounced in the Tg macrophages. Gene expression analysis demonstrated that LPS stimulation significantly increased IL6 and TNF levels in all samples (~4000‐fold and 300‐fold respectively). However, LPS‐induced increase in IL6 expression was significantly attenuated in Tg macrophages (fold elevation compared to vehicle treated: WT 273±92; Tg 78±68). There was no difference in LPS‐induced TNF expression in Tg compared to the WT macrophages.CONCLUSIONCombined these data indicated that CTRP3 attenuates the ability of LPS to activate the pro‐inflammatory functions of the macrophages. Future studies are needed to confirm these findings and to determine the unique mechanism for the CTRP3‐induced alterations to macrophages. Regardless, CTRP3 is a unique contributor to macrophage’s response to inflammatory signals.Support or Funding Information1R15DK114740