Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis

Abstract

Short-chain fatty acid (SCFA) acetate, a byproduct of dietary fiber metabolism by gut bacteria, has multiple immunomodulatory functions. The anti-inflammatory role of acetate is well documented; however, its effect on monocyte chemoattractant protein-1 (MCP-1) production is unknown. Similarly, the comparative effect of SCFA on MCP-1 expression in monocytes and macrophages remains unclear. We investigated whether acetate modulates TNFα-mediated MCP-1/CCL2 production in monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were exposed to acetate with/without TNFα for 24 h, and MCP-1 expression was measured. Monocytes treated with acetate in combination with TNFα resulted in significantly greater MCP-1 production compared to TNFα treatment alone, indicating a synergistic effect. On the contrary, treatment with acetate in combination with TNFα suppressed MCP-1 production in macrophages. The synergistic upregulation of MCP-1 was mediated through the activation of long-chain fatty acyl-CoA synthetase 1 (ACSL1). However, the inhibition of other bioactive lipid enzymes [carnitine palmitoyltransferase I (CPT I) or serine palmitoyltransferase (SPT)] did not affect this synergy. Moreover, MCP-1 expression was significantly reduced by the inhibition of p38 MAPK, ERK1/2, and NF-κB signaling. The inhibition of ACSL1 attenuated the acetate/TNFα-mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB. Increased NF-κB/AP-1 activity, resulting from acetate/TNFα co-stimulation, was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the proinflammatory effects of acetate on TNF-α-mediated MCP-1 production via the ACSL1/MAPK/NF-κB axis in monocytic cells, while a paradoxical effect was observed in THP-1-derived macrophages.

Candida albicans Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis

“…The blots were then washed four times with TBS and incubated for 2 h with HRP-conjugated secondary antibody (Promega, Madison, WI, USA). Immunoreactive bands were developed using an Amersham ECL Plus Western Blotting Detection System (GE Health Care, Buckinghamshire, UK) and visualized using a Molecular Imager ® ChemiDocTM MP Imaging Systems (Bio-Rad Laboratories, Hercules, CA, USA) [ 24 ].…”

TNF-α Increases IP-10 Expression in MCF-7 Breast Cancer Cells via Activation of the JNK/c-Jun Pathways

“…The cDNA was synthesized using 1 μg of total RNA using a high-capacity cDNA reverse transcription kit (Applied Biosystems, Foster City, CA, USA). Real-time PCR was performed on a 7500 Fast Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) using a TaqManTM Gene Expression Master Mix (Applied Biosystems, Foster City, CA, USA) [ 22 , 23 , 24 ]. Each reaction contained 50 ng cDNA that was amplified with Inventoried TaqMan Gene Expression Assay products (IP-10, Hs00171042_m1; c-Jun, Hs01103582_s1; JNK, Hs01548508_m1; and GAPDH, Hs03929097_g1).…”

Microbiota-derived short-chain fatty acids: Implications for cardiovascular and metabolic disease

“…The study also found that intestinal administration of butyrate reduced endotoxemia and the development of AS and indicated that intervention measures aimed at increasing the representation of butyrate-producing bacteria may provide protection against AS ( 55 ). SCFA can also exert its anti-inflammatory effects by interfering with the activation of key signaling proteins, including the MAPK protein ERK (extracellular regulated protein kinase), and can exert its anti-atherosclerotic effects by inhibiting systemic inflammation ( 56 ). In terms of the pathological mechanisms of butyrate-modulated inflammation, Kasahara unraveled that butyrate significantly lowered gut permeability, as well as plasma LPS levels.…”