期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 311, 期 2, 页码 L255-L269出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00218.2015
关键词
adiponectin; reactive oxygen species; cytosolic phospholipase A(2); cyclooxygenase-2; AdipoR
资金
- Shin Kong Wu Ho-Su Memorial Hospital, Taiwan [100-SKH-FJU-12]
- Fu Jen Catholic University Research Foundation, Taiwan [9991A01]
- Ministry of Science and Technology, Taiwan [MOST103-2321-B-182-006, NSC 101-2313-B-030-007]
- Ministry of Education, Taiwan [EMRPD1D0231]
- Chang Gung Medical Research Foundation, Taiwan [CMRPD1C0102]
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 A(2) (cPLA(2)), 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 cPLA(2) 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, Go 6976, and rottlerin), and p300 (garcinol). Briefly, we reported that adiponectin stimulated cPLA(2) 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 cPLA(2) and COX-2 expression together with intracellular ROS production. Understanding the adiponectin signaling pathways on regulating cPLA(2) and COX-2 may help develop therapeutic strategies on pulmonary diseases.
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