Dataset Information

MIP-1? Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-? Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress.

ABSTRACT: Metabolic inflammation is associated with increased expression of saturated free fatty acids, proinflammatory cytokines, chemokines, and adipose oxidative stress. Macrophage inflammatory protein (MIP)-1? recruits the inflammatory cells such as monocytes, macrophages, and neutrophils in the adipose tissue; however, the mechanisms promoting the MIP-1? expression remain unclear. We hypothesized that MIP-1? co-induced by palmitate and tumor necrosis factor (TNF)-? in monocytic cells/macrophages could be further enhanced in the presence of reactive oxygen species (ROS)-mediated oxidative stress. To investigate this, THP-1 monocytic cells and primary human macrophages were co-stimulated with palmitate and TNF-? and mRNA and protein levels of MIP-1? were measured by using quantitative reverse transcription, polymerase chain reaction (qRT-PCR) and commercial enzyme-linked immunosorbent assays (ELISA), respectively. The cognate receptor of palmitate, toll-like receptor (TLR)-4, was blunted by genetic ablation, neutralization, and chemical inhibition. The involvement of TLR4-downstream pathways, interferon regulatory factor (IRF)-3 or myeloid differentiation (MyD)-88 factor, was determined using IRF3-siRNA or MyD88-deficient cells. Oxidative stress was induced in cells by hydrogen peroxide (H2O2) treatment and ROS induction was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. The data show that MIP-1? gene/protein expression was upregulated in cells co-stimulated with palmitate/TNF-? compared to those stimulated with either palmitate or TNF-? (P < 0.05). Further, TLR4-IRF3 pathway was implicated in the cooperative induction of MIP-1? in THP-1 cells, and this cooperativity between palmitate and TNF-? was clathrin-dependent and also required signaling through c-Jun and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B). Notably, ROS itself induced MIP-1? and could further promote MIP-1? secretion together with palmitate and TNF-?. In conclusion, palmitate and TNF-? co-induce MIP-1? in human monocytic cells via the TLR4-IRF3 pathway and signaling involving c-Jun/NF-?B. Importantly, oxidative stress leads to ROS-driven MIP-1? amplification, which may have significance for metabolic inflammation.

SUBMITTER: Sindhu S

PROVIDER: S-EPMC7465096 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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MIP-1α Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-α Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress.

Sindhu Sardar S Akhter Nadeem N Wilson Ajit A Thomas Reeby R Arefanian Hossein H Al Madhoun Ashraf A Al-Mulla Fahd F Ahmad Rasheed R

Cells 20200729 8

Metabolic inflammation is associated with increased expression of saturated free fatty acids, proinflammatory cytokines, chemokines, and adipose oxidative stress. Macrophage inflammatory protein (MIP)-1α recruits the inflammatory cells such as monocytes, macrophages, and neutrophils in the adipose tissue; however, the mechanisms promoting the MIP-1α expression remain unclear. We hypothesized that MIP-1α co-induced by palmitate and tumor necrosis factor (TNF)-α in monocytic cells/macrophages coul ...[more]

PMID: 32751118

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Project description:BackgroundThe association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China.MethodsThe serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case-control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein-Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test.ResultsThe levels of serum macrophage inflammatory protein (MIP)-1α and MIP-1β in the highest categories were associated with a decreased risk of NPC in both the case-control study (MIP-1α: OR = 0.49, 95% CI = 0.26-0.95; MIP-1β: OR = 0.47, 95% CI = 0.22-1.00) and the nested case-control study (MIP-1α: OR = 0.13, 95% CI = 0.03-0.62; MIP-1β: OR = 0.20, 95% CI = 0.04-0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study (MIP-1α: OR = 16.28, 95% CI = 7.11-37.23; MIP-1β: OR = 12.86, 95% CI = 5.9-28.05) and the nested case-control study (MIP-1α: OR = 86.12, 95% CI = 10.58-701.03; MIP-1β: OR = 115.44, 95% CI = 13.92-957.73).ConclusionsDecreased preclinical MIP-1α and MIP-1β levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.

Dataset Information

MIP-1? Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-? Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress.

Publications

MIP-1α Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-α Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress.

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