PMID- 34299302
OWN - NLM
STAT- MEDLINE
DCOM- 20210806
LR  - 20210806
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 14
DP  - 2021 Jul 19
TI  - Short Chain Fatty Acid Acetate Increases TNFalpha-Induced MCP-1 Production in 
      Monocytic Cells via ACSL1/MAPK/NF-kappaB Axis.
LID - 10.3390/ijms22147683 [doi]
LID - 7683
AB  - 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 TNFalpha-mediated MCP-1/CCL2 production in 
      monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were 
      exposed to acetate with/without TNFalpha for 24 h, and MCP-1 expression was measured. 
      Monocytes treated with acetate in combination with TNFalpha resulted in significantly 
      greater MCP-1 production compared to TNFalpha treatment alone, indicating a 
      synergistic effect. On the contrary, treatment with acetate in combination with 
      TNFalpha 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-kappaB signaling. The inhibition of ACSL1 
      attenuated the acetate/TNFalpha-mediated phosphorylation of p38 MAPK, ERK1/2, and 
      NF-kappaB. Increased NF-kappaB/AP-1 activity, resulting from acetate/TNFalpha co-stimulation, 
      was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the 
      proinflammatory effects of acetate on TNF-alpha-mediated MCP-1 production via the 
      ACSL1/MAPK/NF-kappaB axis in monocytic cells, while a paradoxical effect was observed 
      in THP-1-derived macrophages.
FAU - Al-Roub, Areej
AU  - Al-Roub A
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Akhter, Nadeem
AU  - Akhter N
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Al-Sayyar, Amnah
AU  - Al-Sayyar A
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Wilson, Ajit
AU  - Wilson A
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Thomas, Reeby
AU  - Thomas R
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Kochumon, Shihab
AU  - Kochumon S
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Al-Rashed, Fatema
AU  - Al-Rashed F
AUID- ORCID: 0000-0002-5825-7701
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Al-Mulla, Fahd
AU  - Al-Mulla F
AUID- ORCID: 0000-0001-5409-3829
AD  - Genetics & Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait.
FAU - Sindhu, Sardar
AU  - Sindhu S
AUID- ORCID: 0000-0001-9936-1575
AD  - Animal and Imaging Core Facilities, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
FAU - Ahmad, Rasheed
AU  - Ahmad R
AUID- ORCID: 0000-0001-5746-0743
AD  - Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, 
      Kuwait.
LA  - eng
GR  - RA-AML-2014-016 and RA AH 2016-007./Kuwait Foundation for the Advancement of 
      Sciences/
PT  - Journal Article
DEP - 20210719
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Acetates)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Fatty Acids, Volatile)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (TNF protein, human)
RN  - 0 (Triazenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 6M6D4602I5 (triacsin C)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.3 (ACSL1 protein, human)
SB  - IM
MH  - Acetates/administration & dosage/*pharmacology
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Coenzyme A Ligases/antagonists & inhibitors/metabolism
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Fatty Acids, Volatile/administration & dosage/*pharmacology
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Models, Biological
MH  - Monocytes/*drug effects/immunology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Obesity/etiology/metabolism
MH  - Phosphorylation
MH  - RNA, Messenger/genetics/metabolism
MH  - THP-1 Cells
MH  - Triazenes/pharmacology
MH  - Tumor Necrosis Factor-alpha/administration & dosage/pharmacology
PMC - PMC8304091
OTO - NOTNLM
OT  - AP-1
OT  - MCP-1
OT  - NF-kappaB
OT  - THP-1 monocytic cells
OT  - TNFalpha
OT  - acetate
OT  - short-chain fatty acids
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/25 06:00
MHDA- 2021/08/07 06:00
PMCR- 2021/07/19
CRDT- 2021/07/24 01:03
PHST- 2021/06/16 00:00 [received]
PHST- 2021/07/06 00:00 [revised]
PHST- 2021/07/09 00:00 [accepted]
PHST- 2021/07/24 01:03 [entrez]
PHST- 2021/07/25 06:00 [pubmed]
PHST- 2021/08/07 06:00 [medline]
PHST- 2021/07/19 00:00 [pmc-release]
AID - ijms22147683 [pii]
AID - ijms-22-07683 [pii]
AID - 10.3390/ijms22147683 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jul 19;22(14):7683. doi: 10.3390/ijms22147683.