title: Down-regulation of inducible nitric oxide synthase by lysophosphatidic acid in human respiratory epithelial cells.
abstract: Viral infection generally results in the activation of inducible nitric oxide synthase (iNOS or NOS2) in respiratory epithelial cells by inflammatory cytokines. Activated NOS2 catalyzes synthesis of nitric oxide (NO), which in excess can cause cellular injury. On the other hand, lysophosphatidic acid (LPA), a lipid mediator released from epithelial cells, platelets, and fibroblasts in injured tissue, functions in repair of cell injury. However, details of the mechanism for repair by LPA remain unknown. We demonstrated one effect of LPA favoring repair, specifically inhibition by LPA of cytokine-induced NOS2 protein and mRNA expression by human respiratory epithelial cells in vitro. NO production by LPA-treated, cytokine-stimulated cells was also reduced. These decreases were prevented by Rho kinase inhibition with Y-27632. Thus, down-regulation by LPA of cytokine-induced increases in NOS2 activity is likely to involve a Rho-dependent signaling pathway. Harmful biologic effects of NO in viral respiratory infection might be modified by therapeutic manipulations involving LPA or Rho.
authors.affiliation: Division of Internal Medicine and Molecular Therapeutics, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago Tottori, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kadowaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Chikumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yoneda
authors.forename: Akira
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Kenzo
authors.initials: K
authors.lastname: Sato
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000201:enzymology* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007249:Inflammation; D008246:Lysophospholipids / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D012038:Regeneration; D012137:Respiratory System / Q000166:cytology*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000502:physiology
chemical_list: D016207:Cytokines; D008246:Lysophospholipids; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D020741:rho GTP-Binding Proteins; C032881:lysophosphatidic acid