LPS Induces GM-CSF Production by Breast Cancer MDA-MB-231 Cells via Long-Chain Acyl-CoA Synthetase 1

Al-Rashed, Fatema; Thomas, Reeby; Al-Roub, Areej; Al-Mulla, Fahd; Ahmad, Rasheed

doi:10.3390/molecules25204709

Cited by 22 publications

(18 citation statements)

References 28 publications

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“…The data showed that the inhibition of MAPK and NF- κ B suppressed the synergistic effect of acetate/TNFα on the production of MCP-1. Moreover, long-chain acyl-CoA has been shown to induce inflammation through MAPK/NF-κB activation [ 19 , 26 , 27 ]. Therefore, we determined whether ACSL1 had an impact on the acetate/TNFα-mediated phosphorylation of JNK, P38, ERK, and NF-κB.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibiting ACSL1 in monocytes suppressed the TNF-α-induced expression of CD11c, which is a highly expressed inflammatory marker on monocytes and macrophages during conditions of obesity [ 19 ]. ACSL1 regulates the TNFα- and LPS-induced GM-CSF production in breast cancer MDA-MB-231 cells [ 26 , 27 ], suggesting the role of ACSL1 in the regulation of growth-modulating cytokines or embryokines. Increased ACSL1 expression was detected in inflammatory macrophages from obese mice and humans [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

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

Al-Roub

Akhter

Al-Sayyar

et al. 2021

IJMS

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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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Al-Roub

Akhter

Al-Sayyar

et al. 2021

IJMS

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“…Total RNA was extracted using RNeasy Mini Kit (Qiagen, Valencia, CA, USA) per the manufacturer’s instructions. cDNA was synthesized from 1 μg of total RNA using high-capacity cDNA Reverse Transcription Kits (Applied Biosystems, Foster City, CA, USA) [ 17 , 18 ]. Quantitative real-time PCR (qRT-PCR) was performed on a 7500 Fast Real-Time PCR System (Applied Biosystems) using TaqMan ® Gene Expression Master Mix (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by opportunistic pathogens. Candida albicans is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by C. albicans in macrophage foaming and the associated inflammation is poorly understood. We investigated whether C. albicans induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed C. albicans (HKCA). HKCA-induced lipid accumulation in macrophages along with increased expression of inflammatory markers, including CD11b and CD11c or expression and secretion of IL-1β. HKCA also increased the expression of PPARγ, CD36, and FABP4 in macrophages. Mechanistically, we found that the foamy and inflammatory macrophage phenotype induced by HKCA requires FABP4 because disruption of FABP4 in macrophages either by chemical inhibitor BMS309404 or small interfering RNA (siRNA) abrogated foam cell formation and expression of inflammatory markers CD11b, CD11c, and IL-1β. Furthermore, HKCA-treated macrophages displayed high expression and secretion of MMP-9. Inhibition of FABP4 resulted in suppression of HCKA-induced MMP-9 production. Overall, our results demonstrate that C. albicans induces foam cell formation, inflammation, and MMP-9 expression in macrophages via the upregulation of FABP4, which may constitute a novel therapeutic target for treating C. albicans-induced atherosclerosis.

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“…After laser excitation of the samples, optimized emission-detection bandwidths were configured using Zeiss Zen 2012 control software (version 1.1.1.2.0, Gottingen, Germany). Subsequently, confocal images were captured, and fluorescence was measured using Zeiss Zen 2012 software (Gottingen, Germany) [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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IP-10 (also called CXCL10) plays a significant role in leukocyte homing to inflamed tissues, and increased IP-10 levels are associated with the pathologies of various inflammatory disorders, including type 2 diabetes, atherosclerosis, and cancer. TNF-α is a potent activator of immune cells and induces inflammatory cytokine expression in these cells. However, it is unclear whether TNF-α is able to induce IP-10 expression in MCF-7 breast cancer cells. We therefore determined IP-10 expression in TNF-α-treated MCF-7 cells and investigated the mechanism involved. Our data show that TNF-α induced/upregulated the IP-10 expression at both mRNA and protein levels in MCF-7 cells. Inhibition of JNK (SP600125) significantly suppressed the TNF-α-induced IP-10 in MCF-7 cells, while the inhibition of p38 MAPK (SB203580), MEK1/2 (U0126), and ERK1/2 (PD98059) had no significant effect. Furthermore, TNF-α-induced IP-10 expression was abolished in MCF-7 cells deficient in JNK. Similar results were obtained using MCF-7 cells deficient in c-Jun. Moreover, the JNK kinase inhibitor markedly reduced the TNF-α-induced JNK and c-Jun phosphorylation. The kinase activity of JNK induced by TNF-α stimulation of MCF-7 cells was significantly inhibited by SP600125. Altogether, our novel findings provide the evidence that TNF-α induces IP-10 expression in MCF-7 breast cancer cells via activation of the JNK/c-Jun signaling pathway.

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LPS Induces GM-CSF Production by Breast Cancer MDA-MB-231 Cells via Long-Chain Acyl-CoA Synthetase 1

Cited by 22 publications

References 28 publications

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

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

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

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