title: Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin.
abstract: Vasopressin possesses potent anti-inflammatory capacity. Phosphoinositide 3-kinase (PI3K) and its downstream activator Akt contribute to endogenous anti-inflammation capacity. We sought to elucidate whether PI3K is involved in mediating the anti-inflammation effects of vasopressin. Macrophages (RAW264.7 cells) were randomized to receive endotoxin, endotoxin plus vasopressin, or endotoxin plus vasopressin plus the nonselective PI3K inhibitor (LY294002) or the selective isoform inhibitor of PI3Kα (PIK-75), PI3Kβ (TGX-221), PI3Kδ (IC-87114), or PI3Kγ (AS-252424). Compared to macrophages treated with endotoxin, the concentrations of cytokines (tumor necrosis factor-α, interleukin-6) and chemokine (macrophage inflammatory protein-2) in macrophages treated with endotoxin plus vasopressin were significantly lower (all P < 0.05). The concentrations of phosphorylated nuclear factor-κB p65 (p-NF-κB p65) in nuclear extracts and phosphorylated inhibitor-κBα (p-I-κBα) in cytosolic extracts as well as NF-κB-DNA binding activity were also lower (all P < 0.05). Of note, except for macrophages treated with endotoxin plus vasopressin plus PIK-75, the concentrations of cytokines, chemokine, p-NF-κB p65, and p-I-κBα as well as NF-κB-DNA binding activity in macrophages treated with endotoxin plus vasopressin plus LY294002, TGX-221, IC-87114, or AS-252424 were significantly higher than those in macrophages treated with endotoxin plus vasopressin (all P < 0.05). In contrast, the phosphorylated Akt concentration in macrophages treated with endotoxin plus vasopressin was significantly higher than that in macrophages treated with endotoxin or in macrophages treated with endotoxin plus vasopressin plus LY294002, TGX-221, IC-87114, or AS-252424, but not PIK-75. These data confirmed that PI3K, especially the isoforms of PI3Kβ, PI3Kδ, and PI3Kγ, is involved in mediating the anti-inflammatory effects of vasopressin.
authors.affiliation: Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan.
authors.forename: Woan-Ching
authors.initials: WC
authors.lastname: Jan
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Rd., Sindian District, New Taipei City, 231, Taiwan.|School of Medicine, Tzu Chi University, Hualien City, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Kao
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Rd., Sindian District, New Taipei City, 231, Taiwan.|School of Medicine, Tzu Chi University, Hualien City, Taiwan.
authors.forename: Chen-Hsien
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Rd., Sindian District, New Taipei City, 231, Taiwan.|School of Medicine, Tzu Chi University, Hualien City, Taiwan.
authors.forename: Ya-Ying
authors.initials: YY
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Rd., Sindian District, New Taipei City, 231, Taiwan. huangcj1112@gmail.com.|School of Medicine, Tzu Chi University, Hualien City, Taiwan. huangcj1112@gmail.com.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D000067996:RAW 264.7 Cells; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D004731:Endotoxins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; D014667:Vasopressins
keywords: NF-κB; chemokine; cytokine; endotoxin; macrophages; vasopressin