Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis.
Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis.
复制标题
短链脂肪酸乙酸可以通过ACSL1/MAPK/NF-κB轴增加TNFα诱导的单核细胞中MCP-1的产生。
DOI：
10.3390/ijms22147683
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发表时间：
2021-07-19
影响因子：
5.6
通讯作者：
Ahmad R
中科院分区：
文献类型：
--
作者：
Al-Roub A;Akhter N;Al-Sayyar A;Wilson A;Thomas R;Kochumon S;Al-Rashed F;Al-Mulla F;Sindhu S;Ahmad R
短链脂肪酸醋酸酯是肠道细菌代谢膳食纤维的副产物，具有多种免疫调节功能。醋酸盐的抗炎作用已得到充分证实;然而，其对单核细胞趋化蛋白-1（MCP-1）产生的影响尚不清楚。类似地，SCFA对单核细胞和巨噬细胞中MCP-1表达的比较作用仍不清楚。我们研究了醋酸盐是否调节单核细胞/巨噬细胞中TNFα介导的MCP-1/CCL 2的产生，如果是，则通过何种机制。将单核细胞暴露于含/不含TNFα的乙酸24 h，并测量MCP-1表达。与TNFα单独处理相比，用乙酸盐与TNFα联合处理的单核细胞导致显著更高的MCP-1产生，表明协同效应。相反，用乙酸盐与TNFα组合处理抑制巨噬细胞中MCP-1的产生。MCP-1的协同上调是通过激活长链脂肪酰辅酶A合成酶1（ACSL 1）介导的。然而，其他生物活性脂质酶[肉毒碱棕榈酰转移酶I（CPT I）或丝氨酸棕榈酰转移酶（SPT）]的抑制并不影响这种协同作用。此外，通过抑制p38 MAPK、ERK 1/2和NF-κB信号传导，MCP-1表达显著降低。ACSL 1的抑制减弱了乙酸/TNFα介导的p38 MAPK、ERK 1/2和NF-κB的磷酸化。ACSL 1抑制可降低醋酸盐/TNFα共刺激导致的NF-κB/AP-1活性增加。总之，本研究证实了醋酸盐通过ACSL 1/MAPK/NF-κB轴在单核细胞中对TNF-α介导的MCP-1产生的促炎作用，而在THP-1衍生的巨噬细胞中观察到了矛盾的作用。
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.
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影响因子：
4.7
作者：
Kochumon S;Arefanian H;Azim R;Shenouda S;Jacob T;Abu Khalaf N;Al-Rashed F;Hasan A;Sindhu S;Al-Mulla F;Ahmad R
通讯作者：
Ahmad R
影响因子：
3.7
作者：
Ahmad R;Al-Mass A;Al-Ghawas D;Shareif N;Zghoul N;Melhem M;Hasan A;Al-Ghimlas F;Dermime S;Behbehani K
通讯作者：
Behbehani K
影响因子：
4.9
作者：
Kim, C-S;Park, H-S;Yu, R.
通讯作者：
Yu, R.
影响因子：
16.6
作者：
Antunes, Krist Helen;Fachi, Jose Luis;Duarte de Souza, Ana Paula
通讯作者：
Duarte de Souza, Ana Paula
影响因子：
4.9
作者：
Felber, JP;Golay, A
通讯作者：
Golay, A