PMID- 26858641 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160209 LR - 20200930 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 6 DP - 2015 TI - NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-alpha-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion. PG - 310 LID - 10.3389/fphar.2015.00310 [doi] LID - 310 AB - 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-alpha (TNF-alpha), 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-alpha-triggered expression of vascular cell adhesion molecule (VCAM)-1 aggravated the heart inflammation. However, the mechanisms underlying TNF-alpha-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-alpha on VCAM-1 expression. The molecular evidence, including protein, mRNA, and promoter analyses, indicated that TNF-alpha-induced VCAM-1 gene expression is mediated through the TNFR-dependent manner. Activation of TNF-alpha/TNFR system triggered PKCalpha-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-alpha turns on VCAM-1 gene expression. Subsequently, up-regulated VCAM-1 on the cell surface of TNF-alpha-challenged HCFs increased the number of monocytes adhering to these cells. These results indicated that in HCFs, activation of AP-1 by PKCalpha-dependent Nox/ROS/MAPKs cascades is required for TNF-alpha-induced VCAM-1 expression. To clarify the mechanisms of TNF-alpha-induced VCAM-1 expression in HCFs may provide therapeutic strategies for heart injury and inflammatory diseases. FAU - Lin, Chih-Chung AU - Lin CC AD - Department of Anesthetics, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University Tao-Yuan, Taiwan. FAU - Yang, Chien-Chung AU - Yang CC AD - Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung UniversityTao-Yuan, Taiwan; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Lin-KouTao-Yuan, Taiwan. FAU - Wang, Chen-Yu AU - Wang CY AD - Department of Anesthetics, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University Tao-Yuan, Taiwan. FAU - Tseng, Hui-Ching AU - Tseng HC AD - Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University Tao-Yuan, Taiwan. FAU - Pan, Chih-Shuo AU - Pan CS AD - Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University Tao-Yuan, Taiwan. FAU - Hsiao, Li-Der AU - Hsiao LD AD - Department of Anesthetics, Chang Gung Memorial Hospital at Linkou, and College of Medicine, Chang Gung University Tao-Yuan, Taiwan. FAU - Yang, Chuen-Mao AU - Yang CM AD - Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung UniversityTao-Yuan, Taiwan; Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and TechnologyTao-Yuan, Taiwan. LA - eng PT - Journal Article DEP - 20160128 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC4729888 OTO - NOTNLM OT - NADPH oxidase OT - ROS OT - TNF-alpha OT - VCAM-1 OT - cardiac fibroblasts OT - transcription factor EDAT- 2016/02/10 06:00 MHDA- 2016/02/10 06:01 PMCR- 2016/01/28 CRDT- 2016/02/10 06:00 PHST- 2015/09/07 00:00 [received] PHST- 2015/12/16 00:00 [accepted] PHST- 2016/02/10 06:00 [entrez] PHST- 2016/02/10 06:00 [pubmed] PHST- 2016/02/10 06:01 [medline] PHST- 2016/01/28 00:00 [pmc-release] AID - 10.3389/fphar.2015.00310 [doi] PST - epublish SO - Front Pharmacol. 2016 Jan 28;6:310. doi: 10.3389/fphar.2015.00310. eCollection 2015.