The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IκBα/Nuclear Factor-κB Cascade
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Background: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IκBα)/nuclear factor-kappa B (NF-κB) pathway in RAW 264.7 cells. Methods: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IκBα and nuclear translocation of NF-κB p65 were measured by Western blotting, and IκB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IκBα/NF-κB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. Results: The increase of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IκBα degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-κB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IκBα degradation and NF-κB transcription by AVP was abolished by tolvaptan treatment. Conclusions: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IκBα/NF-κB cascade in mouse macrophages via V2 receptors.
Abstract
Background: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IκBα)/nuclear factor-kappa B (NF-κB) pathway in RAW 264.7 cells. Methods: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IκBα and nuclear translocation of NF-κB p65 were measured by Western blotting, and IκB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IκBα/NF-κB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. Results: The increase of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IκBα degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-κB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IκBα degradation and NF-κB transcription by AVP was abolished by tolvaptan treatment. Conclusions: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IκBα/NF-κB cascade in mouse macrophages via V2 receptors.
참고문헌 (24)
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