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Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin

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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.

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Acknowledgements

This work was supported by grants from the Mackay Junior College of Medicine, Nursing and Management (MKC104R9, awarded to W.C. Jan) and the Taipei Tzu Chi Hospital (TCRD-TPE-105-16, awarded to C.J. Huang).

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Authors and Affiliations

  1. Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan

    Woan-Ching Jan

  2. Department of Anesthesiology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Rd., Sindian District, New Taipei City, 231, Taiwan

    Ming-Chang Kao, Chen-Hsien Yang, Ya-Ying Chang & Chun-Jen Huang

  3. School of Medicine, Tzu Chi University, Hualien City, Taiwan

    Ming-Chang Kao, Chen-Hsien Yang, Ya-Ying Chang & Chun-Jen Huang

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  1. Woan-Ching Jan
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Correspondence to Chun-Jen Huang.

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Jan, WC., Kao, MC., Yang, CH. et al. Phosphoinositide 3-Kinase Is Involved in Mediating the Anti-inflammation Effects of Vasopressin. Inflammation 40, 435–441 (2017). https://doi.org/10.1007/s10753-016-0489-x

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  • DOI: https://doi.org/10.1007/s10753-016-0489-x

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