Adipocyte Fatty Acid-binding Protein Modulates Inflammatory Responses in Macrophages through a Positive Feedback Loop Involving c-Jun NH2-terminal Kinases and Activator Protein-1

• DOI: 10.1074/jbc.m109.097907
• Publication Date: 2010-02-10T05:18:33Z
• Authors: Xiaoyan Hui; Huiying Li; Zhiguang Zhou; Karen S.L. Lam; Yang Xiao; Donghai Wu; Ke Ding; Yu Wang; Paul M. Vanhoutte; Aimin Xu
• Keywords: Proinflammatory cytokine

Adipocyte fatty acid-binding protein (A-FABP) has emerged as an important mediator of inflammation in macrophages. Macrophage-selective ablation A-FABP alone is sufficient to prevent the development high cholesterol diet-induced atherosclerosis apoE-deficient mice. However, precise mechanisms whereby modulates remain elusive. Here, we report that forms a finely tuned positive loop between JNK and activator protein-1 (AP-1) exacerbate lipopolysaccharide (LPS)-induced inflammatory responses Real time PCR luciferase reporter analysis showed LPS induced expression through transcriptional activation. This effect was mediated by JNK, which promoted recruitment c-Jun highly conserved AP-1 consensus binding motif located within proximal region promoter. LPS-induced transactivation gene diminished either pharmacological inhibition or knocking down mutating recognition site (-122 -116 bp) Conversely, LPS-evoked phosphorylation activation AP-1, production pro-inflammatory cytokines were markedly attenuated genetic suppression Furthermore, elevation could also be prevented selective inhibitor BMS309403. These findings support notion represents valid strategy for treating inflammation-related disorders such atherosclerosis.