Fatty acid-binding protein 5 limits the anti-inflammatory response in murine macrophages

The beginning stages of liver damage induced by various etiologies (i.e. high fat diet, alcohol consumption, toxin exposure) are characterized by abnormal accumulation of lipid in liver. Alterations in intracellular lipid transport, storage, and metabolism accompanied by cellular insult within the liver play an important role in the pathogenesis of liver disease, often involving a sustained inflammatory response. The intracellular lipid transporter, fatty acid binding protein 5 (FABP(5)), is highly expressed in macrophages and may play an important role in the hepatic inflammatory response after endotoxin exposure in mice. This study tested the hypothesis that FABP(5) regulates macrophage response to LPS in male C57b1/6 (wild type) and FABP(5) knockout mice, both in vitro and in vivo. Treatment with LPS revealed that loss of FABP(5) enhances the number of hepatic F4/80(+) macrophages in the liver despite limited liver injury. Conversely, FABP(5) knock out mice display higher mRNA levels of anti-inflammatory cytokines IL-10, arginase, YM-1, and Fizz-1 in liver compared to wild type mice. Bone marrow derived macrophages stimulated with inflammatory (LPS and IFN-gamma) or anti-inflammatory (IL-4) mediators also showed significantly higher expression of anti-inflammatory/regulatory factors. These findings reveal a regulatory role of FABP(5) in the acute inflammatory response to LPS-induced liver injury, which is consistent with the principle finding that FABP(5) is a regulator of macrophage phenotype. Specifically, these findings demonstrate that loss of FABP(5) promotes a more anti-inflammatory response. (C) 2015 Elsevier Ltd. All rights reserved.