Dataset Information

NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-?-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion.

ABSTRACT: The inflammation-dependent adhesion molecule expressions are characterized in cardiovascular diseases and myocardial tissue infiltrations. Several pro-inflammatory cytokines are elevated in the acute myocardial injury and infarction. Tumor necrosis factor-? (TNF-?), a pro-inflammatory cytokine, is raised in the injury tissues and inflammatory regions and involved in the pathogenesis of cardiac injury, inflammation, and apoptosis. In fibroblasts, TNF-?-triggered expression of vascular cell adhesion molecule (VCAM)-1 aggravated the heart inflammation. However, the mechanisms underlying TNF-?-mediated VCAM-1 expression in cardiac fibroblasts remain unclear. Here, the primary cultured human cardiac fibroblasts (HCFs) were used to investigate the effects of TNF-? on VCAM-1 expression. The molecular evidence, including protein, mRNA, and promoter analyses, indicated that TNF-?-induced VCAM-1 gene expression is mediated through the TNFR-dependent manner. Activation of TNF-?/TNFR system triggered PKC?-dependent NADPH oxidase (Nox)/reactive oxygen species (ROS) signal linking to MAPK cascades, and then led to activation of the transcription factor, AP-1. Moreover, the results of mRNA and promoter assay demonstrated that c-Jun/AP-1 phosphorylated by TNF-? turns on VCAM-1 gene expression. Subsequently, up-regulated VCAM-1 on the cell surface of TNF-?-challenged HCFs increased the number of monocytes adhering to these cells. These results indicated that in HCFs, activation of AP-1 by PKC?-dependent Nox/ROS/MAPKs cascades is required for TNF-?-induced VCAM-1 expression. To clarify the mechanisms of TNF-?-induced VCAM-1 expression in HCFs may provide therapeutic strategies for heart injury and inflammatory diseases.

SUBMITTER: Lin CC

PROVIDER: S-EPMC4729888 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-α-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion.

Lin Chih-Chung CC Yang Chien-Chung CC Wang Chen-Yu CY Tseng Hui-Ching HC Pan Chih-Shuo CS Hsiao Li-Der LD Yang Chuen-Mao CM

Frontiers in pharmacology 20160128

The inflammation-dependent adhesion molecule expressions are characterized in cardiovascular diseases and myocardial tissue infiltrations. Several pro-inflammatory cytokines are elevated in the acute myocardial injury and infarction. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, is raised in the injury tissues and inflammatory regions and involved in the pathogenesis of cardiac injury, inflammation, and apoptosis. In fibroblasts, TNF-α-triggered expression of vascular cell adhesi ...[more]

PMID: 26858641

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Project description:BackgroundAntcin K, an extract of Antrodia cinnamomea (a medicinal mushroom endemic to Taiwan commonly used in Chinese medicine preparations), inhibits proinflammatory cytokine production and angiogenesis in human rheumatoid arthritis synovial fibroblasts (RASFs), major players in RA disease. Antcin K also inhibits disease activity in mice with collagen-induced arthritis (CIA). Up until now, the effects of Antcin K upon cell adhesion molecules (CAMs) were unknown.MethodsRA and healthy synovial tissue samples (n = 10 in each group) were retrieved from the Gene Expression Omnibus (GEO) database (accession code: GDS5401) to compare CAM and monocyte marker expressions. In addition, synovial tissue samples from six RA patients and six patients undergoing arthroscopy for trauma/joint derangement (healthy controls) were subjected to immunohistochemical (IHC) analysis. mRNA and protein expression levels were analyzed in RASFs using RT-qPCR (Reverse transcription-quantitative polymerase chain reaction) and Western blot. RASFs were incubated with Antcin K and examined for monocyte adherence by fluorescence microscopy. Ankle joint tissue specimens from a CIA mouse model and healthy controls were stained with hematoxylin and eosin (H&E) and Safranin-O/Fast Green to examine histological changes and evidence of bone loss. IHC analysis determined levels of vascular cell adhesion molecule 1 (VCAM-1) and CD11b in CIA ankle tissue and clinical synovial tissue.ResultsLevels of VCAM-1 expression were higher in the GEO database specimens and the study's clinical samples of RA synovial tissue compared with the healthy specimens. Antcin K dose-dependently inhibited VCAM-1 expression and monocyte adhesion in RASFs. Antcin K also significantly inhibited levels of VCAM-1 and monocyte CD11b expression in CIA tissue. These effects appeared to be mediated by MEK1/2-ERK, p38, and AP-1 signaling.ConclusionsAntcin K seems promising for the treatment of RA and deserves further investigations.

Dataset Information

NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-?-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion.

Publications

NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-α-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion.

Similar Datasets

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