Novel anti-inflammatory role of SLPI in adipose tissue and its regulation by high fat diet

Abstract

Background Secretory leucocyte protease inhibitor (SLPI) is an anti-inflammatory protein that is constitutively expressed in multiple cell types where it functions to counteract localized tissue inflammation by its anti-inflammatory, antimicrobial and anti-protease properties. Little is known about the expression and implication of SLPI in the regulation of adipose tissue inflammation. Therefore, we tested the hypothesis that obesity induces expression of SLPI in adipose tissue where it functions to counteract adipocyte inflammation. Methods Male C57BL6 mice were fed a high fat (60% fat calories) or a control diet (10% fat calories) diet for 12 weeks. Adipose tissue expression of SLPI was determined by western blotting and PCR. Fully differentiated adipocytes (3T3-L1) were treated with lipopolysaccharide (LPS, 100 ng/ml) or peptidoglycan (10 μg/ml) for 24 hours in the presence or absence of SLPI. Media was collected for interleukin 6 (IL-6) analysis by enzyme-linked immune absorbent assay (ELISA). RNA was isolated for gene expression analysis by real-time polymerase chain reaction (RT-PCR). Results Visceral fat (mesenteric and epididymal) express a higher level of SLPI than subcutaneous fat. The expression of SLPI is mostly in the stromal vascular fraction compared to adipocytes. We also confirmed in vitro that activation of TLR2 and 4 with peptidoglycan and LPS respectively leads to induction of SLPI. Finally, we confirmed that SLPI exerted an anti-inflammatory effect in adipocytes treated with LPS by causing a reduction in expression of IL-6 via a mechanism that included stabilization of cellular IKBα expression. Conclusion Our results show that SLPI is also expressed in adipocytes and adipose tissue where it could play an important feedback role in the resolution of inflammation.