Effect of Free Fatty Acids on Inflammatory Gene Expression and Hydrogen Peroxide Production by Ex Vivo Blood Mononuclear Cells

Sureda, Antoni; Martorell, Miquel; Bibiloni, María del Mar; Bouzas, Cristina; Gallardo-Alfaro, Laura; Matéos, David; Capó, Xavier; Tur, Josep A.; Pons, Antoni

doi:10.3390/nu12010146

Cited by 19 publications

(20 citation statements)

References 62 publications

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“…IL-6 also plays important roles at different stages of inflammation. For example, significant quantities of IL-6 are secreted by monocytes and macrophages at the early stage of infectious inflammation and participates in host immune defense (28). Furthermore, IL-6 participates in humoral immune regulation by regulating B cell functions (29).…”

Section: Discussionmentioning

confidence: 99%

IL‑6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac

Jia

Cui

et al. 2021

Exp Ther Med

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The aim of the present study was to investigate the effect of the IL-6/STAT3 signaling pathway on intestinal epithelial barrier injury in patients with ulcerative colitis (UC). Fifty-two patients with UC and 21 healthy subjects were recruited. The expression level of IL-6 in plasma was determined by ELISA. Normal human colon mucosal epithelial NCM460 cells were treated with IL-6 or plasma from the patients with UC. Then, the transepithelial electrical resistance value, fluorescein yellow permeability and zonulin release were evaluated. Using reverse transcription-quantitative (q)PCR and western blotting, claudin (CLDN) 1 and CLDN2 expression levels were analyzed. Furthermore, western blotting was used to detect phosphorylation of STAT3. Chromatin immunoprecipitation-qPCR was performed to investigate the enrichment of H3K27ac in the promoter regions of CLDN1 and CLDN2. The present study revealed that IL-6 content was elevated in the plasma from patients with UC and increased with the progression of the disease. IL-6 was also observed to induce intestinal epithelial cell barrier injury and regulate barrier function by influencing the expression of tight junction-related proteins, as well as STAT3. The IL-6/STAT3 signaling pathway regulated transcription of CLDN1 and CLDN2 by affecting the enrichment of histone H3K27ac in their promoter regions. Thus, the significantly increased expression level of IL-6 in the peripheral blood of patients with UC indicates a positive association with the development of UC. Furthermore, the IL-6/STAT3 signaling pathway influences the function of the intestinal barrier by affecting the H3K27ac level in intestinal epithelial cells.

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Section: Discussionmentioning

confidence: 99%

IL‑6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac

Jia

Cui

et al. 2021

Exp Ther Med

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“…PMA, a molecular mimetic of diacylglycerol [63] used to activate immune cells by mimicking their response to acute exercise [64], activates several isoforms of protein kinase C (PKC), particularly PKCδ and ε, which in turn activate the NFκB signaling pathway [65]. Both LPS and PMA can increase ROS production in immune cells by the assembly and activation of NADPH-oxidases or by the activation of mitochondrial respiratory chain function [30,64,[66][67][68]. Moreover, both PMA and LPS increase antioxidant enzyme gene expression in PBMCs [30], neutrophils [69,70] and HL60 cells [64].…”

Section: Discussionmentioning

confidence: 99%

“…Both LPS and PMA can increase ROS production in immune cells by the assembly and activation of NADPH-oxidases or by the activation of mitochondrial respiratory chain function [30,64,[66][67][68]. Moreover, both PMA and LPS increase antioxidant enzyme gene expression in PBMCs [30], neutrophils [69,70] and HL60 cells [64]. The intake of a nitrate-rich beverage influences the antioxidant and pro-inflammatory gene expression profile after the immune stimulation of PBMCs from metabolic syndrome patients with PMA or LPS.…”

Section: Discussionmentioning

confidence: 99%

“…The mRNA expression of the genes detailed in Supplementary Table S1 was determined by real time polymerase chain reaction (RT-PCR) with human 18S ribosomal as the reference gene. Total RNA was purified from PBMCs by Tripure extraction (Roche Diagnostics, Mannheim, Germany) following a procedure previously described [30]. The isolated RNA (1 µg) from each subject was reversely transcribed using Expand Reverse Transcriptase (50 U) (Roche Diagnostics, Mannheim, Germany) for 60 min at 42 • C and 5 min at 99 • C in a final volume of 10 µL, according to the manufacturer's instructions.…”

Section: Pbmcs Rna Extraction and Real-time Pcr Assaymentioning

confidence: 99%

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Dietary Sodium Nitrate Activates Antioxidant and Mitochondrial Dynamics Genes after Moderate Intensity Acute Exercise in Metabolic Syndrome Patients

Ferrer

Capó

Reynés

et al. 2021

JCM

Self Cite

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Exercise can induce a pro-inflammatory response in aged subjects with metabolic disorders and nitrate supplementation has shown anti-inflammatory effects. We evaluated the influence of dietary nitrate on the response of the antioxidant and mitochondrial dynamics genes to acute exercise in peripheral blood mononuclear cells (PBMCs), as well as the antioxidant and the inflammatory response of PBMCs against immune stimulation. Metabolic syndrome patients participated in a crossover study in which they consumed a beverage containing 16 mM sodium nitrate or a placebo with the same composition without nitrate before performing a submaximal test at 60%–70% of their maximal heart rate for 30 min. The intake of nitrate increased the nitrate plus nitrite plasma levels about 8-fold and induced the upregulation of catalase, superoxide dismutase, glutathione peroxidase, mitofusin 2 and PGC1α in PBMCs after exercise. The gene expression of catalase and TNFα was enhanced by phorbol myristate acetate (PMA) only in the placebo group, while the glutathione peroxidase expression was enhanced by PMA only after nitrate intake. The intake of nitrate by metabolic syndrome patients induces an antioxidant and mitochondrial response to exercise at the same time that it attenuates the pro-inflammatory response to immune stimulation.

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“…Finally, saturated and unsaturated FA were also shown to differentially influence inflammatory gene expression in LPS-stimulated PBMC [ 130 , 131 ]. MUFA and ω3 PUFA reduce inflammatory gene expression, by influencing NF-κB cell availability and modifying its post-translational regulation.…”

Section: Fatty Acids and Immune Cells: Regulation Of Transcription Factors Inflammatory Pathways And Effector Functionsmentioning

confidence: 99%

Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response

Cornò

Varì

Scazzocchio

et al. 2021

Cells

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Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.

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Effect of Free Fatty Acids on Inflammatory Gene Expression and Hydrogen Peroxide Production by Ex Vivo Blood Mononuclear Cells

Cited by 19 publications

References 62 publications

IL‑6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac

IL‑6/STAT3 signaling pathway regulates the proliferation and damage of intestinal epithelial cells in patients with ulcerative colitis via H3K27ac

Dietary Sodium Nitrate Activates Antioxidant and Mitochondrial Dynamics Genes after Moderate Intensity Acute Exercise in Metabolic Syndrome Patients

Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response

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