Growing evidence for a role for acyl-CoA synthetase 1 in immunometabolism

Bornfeldt, Karin E.

doi:10.1002/jlb.3ce0519-154r

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…Emerging evidence suggests that ACSL1 is involved in TNFα mediated immune regulation [16,18]. We therefore examined whether ACSL1 was required for TNFα induced GM-CSF production by MDA-MB-231 cells, and we used triacsin C to inhibit ACSL1 activity in MDA-MB-231 cells and measured the GM-CSF.…”

Section: Resultsmentioning

confidence: 99%

ACSL1 Regulates TNFα-Induced GM-CSF Production by Breast Cancer MDA-MB-231 Cells

et al. 2019

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Overexpression of granulocyte-macrophage colony-stimulating factor (GM-CSF) in different types of cancer is associated with tumor growth and progression. Tumor necrosis factor-α (TNFα) is involved in the induction of GM-CSF in different cells; however, the underlying molecular mechanism in this production of GM-CSF has not been fully revealed. Recently, it was noted that TNFα mediates inflammatory responses through long-chain acyl-CoA synthetase 1 (ACSL1). Therefore, we investigated the role of ACSL1 in the TNFα mediated production of GM-CSF. Our results showed that MDA-MB-231 cells displayed increased GM-CSF mRNA expression and secretion after incubation with TNFα. Blocking of ACSL1 activity in the cells with triacsin C markedly suppressed the secretion of GM-CSF. However, inhibition of β-oxidation and ceramide biosynthesis were not required for GM-CSF production. By small interfering RNA mediated knockdown, we further demonstrated that TNFα induced GM-CSF production was significantly diminished in ACSL1 deficient cells. TNFα mediated GM-CSF expression was significantly reduced by inhibition of p38 MAPK, ERK1/2 and NF-κB signaling pathways. TNFα induced phosphorylation of p38, ERK1/2, and NF-κB was observed during the secretion of GM-CSF. On the other hand, inhibition of ACSL1 activity attenuates TNFα mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB in the cells. Importantly, our findings suggest that ACSL1 plays an important role in the regulation of GM-CSF induced by TNFα in MDA-MB-231 cells. Therefore, ACSL1 may be considered as a potential novel therapeutic target for tumor growth.

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Section: Resultsmentioning

confidence: 99%

ACSL1 Regulates TNFα-Induced GM-CSF Production by Breast Cancer MDA-MB-231 Cells

et al. 2019

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“…Accumulating evidence suggests that ACSL1 participates in TNFα-mediated immune regulation 16 , 32 . We, therefore, investigated whether ACSL1 was involved in TNFα- mediated MMP-9 production by THP-1 cells.…”

Section: Resultsmentioning

confidence: 99%

TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/ERK/NF-kB signaling pathways

Al-Roub,

Akhter,

Al-Rashed

et al. 2023

Sci Rep

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Studies have established the association between increased plasma levels of matrix metalloproteinase (MMP)-9 and adipose tissue inflammation. Tumor necrosis factor α (TNFα) was elevated in obesity and is involved in the induction of MMP-9 in monocytic cells. However, the underlying molecular mechanism was incompletely understood. As per our recent report, TNFα mediates inflammatory responses through long-chain acyl-CoA synthetase 1 (ACSL1). Therefore, we further investigated the role of ACSL1 in TNFα-mediated MMP-9 secretion in monocytic cells. THP-1 cells and primary monocytes were used to study MMP-9 expression. mRNA and protein levels of MMP-9 were determined by qRT-PCR and ELISA, respectively. Signaling pathways were studied using Western blotting, inhibitors, and NF-kB/AP1 reporter cells. We found that THP-1 cells and primary human monocytes displayed increased MMP-9 mRNA expression and protein secretion after incubation with TNFα. ACSL1 inhibition using triacsin C significantly reduced the expression of MMP-9 in the THP-1 cells. However, the inhibition of β-oxidation and ceramide biosynthesis did not affect the TNFα-induced MMP-9 production. Using small interfering RNA-mediated ACSL1 knockdown, we further confirmed that TNFα-induced MMP-9 expression/secretion was significantly reduced in ACSL1-deficient cells. TNFα-mediated MMP-9 expression was also significantly reduced by the inhibition of ERK1/ERK2, JNK, and NF-kB. We further observed that TNFα induced phosphorylation of SAPK/JNK (p54/46), ERK1/2 (p44/42 MAPK), and NF-kB p65. ACSL1 inhibition reduced the TNFα-mediated phosphorylation of SAPK/JNK, c-Jun, ERK1/2, and NF-kB. In addition, increased NF-κB/AP-1 activity was inhibited in triacsin C treated cells. Altogether, our findings suggest that ACSL1/JNK/ERK/NF-kB axis plays an important role in the regulation of MMP-9 induced by TNFα in monocytic THP-1 cells.

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“…TNFα-Induced MMP-9 Production is Suppressed by the Inhibition of ACSL1 Accumulating evidence suggests that ACSL1 participates in TNFα-mediated immune regulation 16,32 . We, therefore, investigated whether ACSL1 was involved in TNFα-mediated MMP-9 production by THP-1 cells.…”

Section: Tnfα Induced Mmp-9 Gene Expression In Human Monocytes and Ma...mentioning

confidence: 99%

TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/NF- kB signaling pathways

Al-Roub

Akhter

Al-Rashed

et al. 2023

Preprint

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Background Studies have established the association between increased plasma levels of matrix metalloproteinase (MMP)-9 and adipose tissue inflammation. Tumor necrosis factor α (TNFα) was elevated in obesity and is involved in the induction of MMP-9 in monocytic cells. However, the underlying molecular mechanism was incompletely understood. As per our recent report, TNFα mediates inflammatory responses through long-chain acyl-CoA synthetase 1 (ACSL1). Therefore, we further investigated the role of ACSL1 in TNFα-mediated MMP-9 secretion in monocytic cells and macrophages. Methods Monocytic THP-1 cells and macrophages were used to study MMP-9 expression. mRNA and protein levels of MMP-9 were determined by qRT-PCR and ELISA, respectively, and its biological activity was determined by zymography. Signaling pathways were studied using Western blotting, inhibitors, and NF-kB/AP1 reporter cells. Results We found that THP-1 monocytic cells and macrophages displayed increased MMP-9 mRNA expression, as well as biologically active protein secretion after incubation with TNFα. Inhibition of ACSL1 in the cells with triacsin C significantly reduced MMP-9 secretion. However, inhibition of β-oxidation and ceramide biosynthesis was not affected by TNFα-induced MMP-9 production. Using small interfering RNA-mediated knockdown, we further confirmed that TNFα-induced MMP-9 secretion was significantly reduced in ACSL1-deficient cells. Moreover, TNFα-mediated MMP-9 expression was significantly reduced by inhibition of ERK1/ERK2, JNK, and NF-kB signaling pathways. We further observed TNFα-induced phosphorylation of JNK, ERK1/ERK2, and NF-kB. On the other hand, inhibition of ACSL1 reduced TNFα-mediated phosphorylation of JNK, c-Jun, ERK1/2, and NF-kB in THP-1 monocytic cells. In addition, increased NF-κB/AP-1 activity was inhibited in triacsin C-treated cells. Conclusion Altogether, our findings suggest that ACSL1/JNK/ ERK/NF-kB axis plays an important role in the regulation of MMP-9 induced by TNFα in monocytic THP-1 cells and macrophages.

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Growing evidence for a role for acyl-CoA synthetase 1 in immunometabolism

Abstract: Discussion on the role of acyl‐CoA synthetase 1 in immunometabolism.

Cited by 5 publications

References 10 publications

ACSL1 Regulates TNFα-Induced GM-CSF Production by Breast Cancer MDA-MB-231 Cells

ACSL1 Regulates TNFα-Induced GM-CSF Production by Breast Cancer MDA-MB-231 Cells

TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/ERK/NF-kB signaling pathways

TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/NF- kB signaling pathways

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