AdipoR-increased intracellular ROS promotes cPLA2 and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells.
Adiponectin, an adipokine, accumulated in lung system via T-cadherin after allergens/ozone challenge. However, the roles of adiponectin on lung pathologies were controversial. Here we reported that adiponectin stimulated expression of inflammatory proteins, cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of reactive oxygen species (ROS) in human alveolar type II A549 cells. AdipoR1/2 involved in adiponectin-activated NADPH oxidase and mitochondria, which further promoted intracellular ROS accumulation. Protein kinase C (PKC) may involve an adiponectin-activated NADPH oxidase. Similarly, p300 phosphorylation and histone H4 acetylation occurred in adiponectin-challenged A549 cells. Moreover, adiponectin-upregulated cPLA2 and COX-2 expression was significantly abrogated by ROS scavenger (N-acetylcysteine) or the inhibitors of NADPH oxidase (apocynin), mitochondrial complex I (rotenone), PKC (Ro31-8220, Gö-6976, and rottlerin), and p300 (garcinol). Briefly, we reported that adiponectin stimulated cPLA2 and COX-2 expression via AdipoR1/2-dependent activation of PKC/NADPH oxidase/mitochondria resulting in ROS accumulation, p300 phosphorylation, and histone H4 acetylation. These results suggested that adiponectin promoted lung inflammation, resulting in exacerbation of pulmonary diseases via upregulating cPLA2 and COX-2 expression together with intracellular ROS production. Understanding the adiponectin signaling pathways on regulating cPLA2 and COX-2 may help develop therapeutic strategies on pulmonary diseases.
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, Xinzhuang, New Taipei City, Taiwan;
Hsiao-Mei
HM
Chen
Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan; Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo, Kwei-San, Tao-Yuan, Taiwan; Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan;
Chuen-Mao
CM
Yang
PhD Program in Nutrition and Food Science, Fu Jen Catholic University, Xinzhuang, New Taipei City, Taiwan; Department of Internal Medicine, En-Chu-Kong Hospital, Sanxia, New Taipei City, Taiwan.
Jia-Feng
JF
Chang
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, Xinzhuang, New Taipei City, Taiwan;
Chi-Sheng
CS
Wu
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, Xinzhuang, New Taipei City, Taiwan;
Kee-Chin
KC
Sia
Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, Xinzhuang, New Taipei City, Taiwan;
Wei-Ning
WN
Lin
D000072283:A549 Cells; D000107:Acetylation; D052242:Adiponectin / Q000502:physiology*; D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D004789:Enzyme Activation; D004790:Enzyme Induction; D015870:Gene Expression; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D019255:NADPH Oxidases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017382:Reactive Oxygen Species / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000378:metabolism*; D015398:Signal Transduction
C499918:ADIPOQ protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D006657:Histones; D017382:Reactive Oxygen Species; D054419:Receptors, Adiponectin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019255:NADPH Oxidases; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D011493:Protein Kinase C; D054513:Group IV Phospholipases A2
AdipoR; adiponectin; cyclooxygenase-2; cytosolic phospholipase A2; reactive oxygen species