ArticleJournal of immunology (Baltimore, Md. : 1950)2018
The Synergy between Palmitate and TNF-α for CCL2 Production Is Dependent on the TRIF/IRF3 Pathway: Implications for Metabolic Inflammation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 92 citations in OpenAlex.
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- Immune dysregulation in gestational diabetes mellitus: placental downregulation of CXCL9 and IL1RL1 and altered immune cell infiltration.Frontiers in cell and developmental biology · 2026Article
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- Group 1 innate lymphoid cells and inflammatory macrophages exacerbate fibrosis in creeping fat through IFN-γ secretion.Journal of gastroenterology · 2025Article
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- Systems analysis unravels a common rural-urban gradient in immunological profile, function, and metabolic dependencies.Science advances · 2025Article
- TNF-α/NF-κB mediated upregulation of Dectin-1 in hyperglycemic obesity: implications for metabolic inflammation and diabetes.Journal of translational medicine · 2025Article
- Long-chain fatty acids - The turning point between 'mild' and 'severe' acute pancreatitis.Heliyon · 2024Review
- Lysophosphatidic Acid-Mediated Inflammation at the Heart of Heart Failure.Current cardiology reports · 2024Review
- Renal transcriptome analysis of uninephrectomized db/db mice identified a mechanism for the transition to severe diabetic nephropathy.Experimental animals · 2024Article
- The Role of cGAS-STING Signalling in Metabolic Diseases: from Signalling Networks to Targeted Intervention.International journal of biological sciences · 2024Review
- Anti-Inflammatory Mechanisms of Curcumin and Its Metabolites in White Adipose Tissue and Cultured Adipocytes.Nutrients · 2023Article
- Silencing HOXC13 exerts anti-prostate cancer effects by inducing DNA damage and activating cGAS/STING/IRF3 pathway.Journal of translational medicine · 2023Article
- TNFα induces matrix metalloproteinase-9 expression in monocytic cells through ACSL1/JNK/ERK/NF-kB signaling pathways.Scientific reports · 2023Article
- Article
- Chicoric acid ameliorates palmitate-induced sphingosine 1-phosphate signaling pathway in the PBMCs of patients with newly diagnosed type 2 diabetes.Journal of diabetes and metabolic disorders · 2023Article
- Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice.Genes & diseases · 2023Article
- CCL2-Mediated Stromal Interactions Drive Macrophage Polarization to Increase Breast Tumorigenesis.International journal of molecular sciences · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The chemokine CCL2 (also known as MCP-1) is a key regulator of monocyte infiltration into adipose tissue, which plays a central role in the pathophysiology of obesity-associated inflammation and insulin resistance. It remains unclear how CCL2 production is upregulated in obese humans and rodents. Because elevated levels of the free fatty acid (FFA) palmitate and TNF-α have been reported in obesity, we studied whether these agents interact to trigger CCL2 production. Our data show that treatment of THP-1 and primary human monocytic cells with palmitate and TNF-α led to a marked increase in CCL2 production compared with either treatment alone. Mechanistically, we found that cooperative production of CCL2 by palmitate and TNF-α did not require MyD88, but it was attenuated by blocking TLR4 or TRIF. IRF3-deficient cells did not show synergistic CCL2 production in response to palmitate/TNF-α. Moreover, IRF3 activation by polyinosinic-polycytidylic acid augmented TNF-α-induced CCL2 secretion. Interestingly, elevated NF-κB/AP-1 activity resulting from palmitate/TNF-α costimulation was attenuated by TRIF/IRF3 inhibition. Diet-induced C57BL/6 obese mice with high FFAs levels showed a strong correlation between TNF-α and CCL2 in plasma and adipose tissue and, as expected, also showed increased adipose tissue macrophage accumulation compared with lean mice. Similar results were observed in the adipose tissue samples from obese humans. Overall, our findings support a model in which elevated FFAs in obesity create a milieu for TNF-α to trigger CCL2 production via the TLR4/TRIF/IRF3 signaling cascade, representing a potential contribution of FFAs to metabolic inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.