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Open AccessArticle

Stearic Acid and TNF-α Co-Operatively Potentiate MIP-1α Production in Monocytic Cells via MyD88 Independent TLR4/TBK/IRF3 Signaling Pathway

1
Immunology & Microbiology Department, Dasman Diabetes Institute, Kuwait City 15462, Kuwait
2
School of Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Adliya 15503, Bahrain
3
Animal & Imaging Core Facility, Dasman Diabetes Institute, Kuwait City 15462, Kuwait
4
Genetics and Bioinformatics, Dasman Diabetes Institute, Kuwait City 15462, Kuwait
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Biomedicines 2020, 8(10), 403; https://doi.org/10.3390/biomedicines8100403
Received: 7 September 2020 / Revised: 22 September 2020 / Accepted: 7 October 2020 / Published: 9 October 2020
(This article belongs to the Special Issue Macrophages in Health and Non-infectious Disease)
Increased circulatory and adipose tissue expression of macrophage inflammatory protein (MIP)-1α (CC motif chemokine ligand-3/CCL3) and its association with inflammation in the state of obesity is well documented. Since obesity is associated with increases in both stearic acid and tumor necrosis factor α (TNF-α) in circulation, we investigated whether stearic acid and TNF-α together could regulate MIP-1α/CCL3 expression in human monocytic cells, and if so, which signaling pathways were involved in MIP-1α/CCL3 modulation. Monocytic cells were treated with stearic acid and TNF-α resulted in enhanced production of MIP-1α/CCL3 compared to stearic acid or TNF-α alone. To explore the underlying mechanisms, cooperative effect of stearic acid for MIP-α/CCL3 expression was reduced by TLR4 blocking, and unexpectedly we found that the synergistic production of MIP-α/CCL3 in MyD88 knockout (KO) cells was not suppressed. In contrast, this MIP-α/CCL3 expression was attenuated by inhibiting TBK1/IRF3 activity. Cells deficient in IRF3 did not show cooperative effect of stearate/TNF-α on MIP-1α/CCL3 production. Furthermore, activation of IRF3 by polyinosinic-polycytidylic acid (poly I:C) produced a cooperative effect with TNF-α for MIP-1α/CCL3 production that was comparable to stearic acid. Individuals with obesity show high IRF3 expression in monocytes as compared to lean individuals. Furthermore, elevated levels of MIP-1α/CCL3 positively correlate with TNF-α and CD163 in fat tissues from individuals with obesity. Taken together, this study provides a novel model for the pathologic role of stearic acid to produce MIP-1α/CCL3 in the presence of TNF-α associated with obesity settings. View Full-Text
Keywords: MIP-1α; stearic acid; TNF-α/CCL3; TLR4; TRIF/TBK; IRF3; obesity MIP-1α; stearic acid; TNF-α/CCL3; TLR4; TRIF/TBK; IRF3; obesity
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MDPI and ACS Style

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. Stearic Acid and TNF-α Co-Operatively Potentiate MIP-1α Production in Monocytic Cells via MyD88 Independent TLR4/TBK/IRF3 Signaling Pathway. Biomedicines 2020, 8, 403.

AMA Style

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. Stearic Acid and TNF-α Co-Operatively Potentiate MIP-1α Production in Monocytic Cells via MyD88 Independent TLR4/TBK/IRF3 Signaling Pathway. Biomedicines. 2020; 8(10):403.

Chicago/Turabian Style

Kochumon, Shihab; Arefanian, Hossein; Azim, Rafaat; Shenouda, Steve; Jacob, Texy; Abu Khalaf, Nermeen; Al-Rashed, Fatema; Hasan, Amal; Sindhu, Sardar; Al-Mulla, Fahd; Ahmad, Rasheed. 2020. "Stearic Acid and TNF-α Co-Operatively Potentiate MIP-1α Production in Monocytic Cells via MyD88 Independent TLR4/TBK/IRF3 Signaling Pathway" Biomedicines 8, no. 10: 403.

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