Palmitate induces interleukin-8 expression in human monocytic cells via TLR4/MyD88 dependent pathway

Abstract

Abstract Infiltrated immune cells in adipose tissue in obesity produce various cytokines and chemokines which are involved in metabolic inflammation and insulin resistance. Obese individuals are known to have increased IL-8 plasma level and it plays an important role in metabolic disorders. Since in obesity, the levels of circulatory saturated free fatty acid palmitate are increased and modulate the expression of other cytokines and chemokines, the role of palmitate in the regulation of IL-8 in monocytic cells is not well defined. Here, we provide the evidence that palmitate induces IL-8 expression at both mRNA and protein levels in human monocytic cells (P<0.05). Palmitate-mediated IL-8 secretion was suppressed either by neutralizing anti-TLR4 antibody or by genetic silencing of TLR4. Furthermore, MyD88−/− cells did not express IL-8 in response to palmitate. However, IRF3 deficiency did not affect IL-8 production. NF-κB/AP-1 activity was also elevated in palmitate-treated cells. Altogether, these results show that palmitate induces TLR4/MyD88 dependent activation of IL-8 gene expression leading to activation of NF-kB/AP1 transcription factors.