VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production

Mizuho Kojima, Tetsuhide Ito, takamasa ono, Terumasa Hisano, Hisato Igarashi, Yoshiyuki Arita, Ken Kawabe, David H. Coy, Robert T. Jensen, Hajime Nawata

研究成果: ジャーナルへの寄稿記事

37 引用 (Scopus)

抄録

Objectives: VIP receptor has been clarified to exist on immune cells, indicating its possible involvement in immunity and inflammatory response. Therefore, we investigated the effects of VIP and selective agonists for 2 subtypes of VIP receptor (VPAC1-R and VPAC2-R agonist) on acute pancreatitis. Methods: Acute pancreatitis was induced in mice by 4 intraperitoneal injections of cerulein and an injection of LPS. VIP, VPAC 1-R agonist, VPAC2-R agonist, or secretin (5 nmol/body) was administered 30 minutes before and after the administration of LPS. Serum amylase and cytokine levels were determined, and histologic changes were evaluated. In vitro, IL-6 and TNF-α production by monocytes from the spleen was determined under the stimulation of LPS with VIP, VPAC1-R agonist, or VPAC2-R agonist, and the expression of VPAC1-R and VPAC2-R mRNA in monocytes was examined. Results: VPAC 1-R agonist significantly decreased serum amylase, IL-6, and TNF-α, whereas VPAC2-R agonist markedly increased serum amylase. Histologically, VIP and VPAC1-R agonist attenuated the severity of pancreatitis, although VPAC2-R agonist or secretin showed no significant effect. In vitro, VPAC1-R and VPAC2-R mRNA were obviously expressed in monocytes. Under the stimulation with LPS, VIP presented a biphasic pattern that once decreased IL-6 production from monocytes and then enhanced at high concentration. VPAC1-R agonist reduced IL-6 levels, whereas VPAC2-R agonist increased IL-6 dose-dependently. VPAC1-R agonist reduced TNF-α levels in a dose-dependent manner. Conclusion: VIP attenuated the experimental acute pancreatitis enzymatically and morphologically by inhibiting proinflammatory cytokine production from monocytes mainly through the VPAC1-R.

元の言語英語
ページ(範囲)62-70
ページ数9
ジャーナルPancreas
30
発行部数1
出版物ステータス出版済み - 1 1 2005

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Receptors, Vasoactive Intestinal Polypeptide, Type I
Pancreatitis
Monocytes
Interleukin-6
Cytokines
Amylases
Vasoactive Intestinal Peptide Receptors
Secretin
Serum
Ceruletide
Messenger RNA
Intraperitoneal Injections
Immunity
Spleen
Injections

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

これを引用

Kojima, M., Ito, T., ono, T., Hisano, T., Igarashi, H., Arita, Y., ... Nawata, H. (2005). VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production. Pancreas, 30(1), 62-70.

VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production. / Kojima, Mizuho; Ito, Tetsuhide; ono, takamasa; Hisano, Terumasa; Igarashi, Hisato; Arita, Yoshiyuki; Kawabe, Ken; Coy, David H.; Jensen, Robert T.; Nawata, Hajime.

:: Pancreas, 巻 30, 番号 1, 01.01.2005, p. 62-70.

研究成果: ジャーナルへの寄稿記事

Kojima, M, Ito, T, ono, T, Hisano, T, Igarashi, H, Arita, Y, Kawabe, K, Coy, DH, Jensen, RT & Nawata, H 2005, 'VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production', Pancreas, 巻. 30, 番号 1, pp. 62-70.
Kojima, Mizuho ; Ito, Tetsuhide ; ono, takamasa ; Hisano, Terumasa ; Igarashi, Hisato ; Arita, Yoshiyuki ; Kawabe, Ken ; Coy, David H. ; Jensen, Robert T. ; Nawata, Hajime. / VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production. :: Pancreas. 2005 ; 巻 30, 番号 1. pp. 62-70.
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title = "VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production",
abstract = "Objectives: VIP receptor has been clarified to exist on immune cells, indicating its possible involvement in immunity and inflammatory response. Therefore, we investigated the effects of VIP and selective agonists for 2 subtypes of VIP receptor (VPAC1-R and VPAC2-R agonist) on acute pancreatitis. Methods: Acute pancreatitis was induced in mice by 4 intraperitoneal injections of cerulein and an injection of LPS. VIP, VPAC 1-R agonist, VPAC2-R agonist, or secretin (5 nmol/body) was administered 30 minutes before and after the administration of LPS. Serum amylase and cytokine levels were determined, and histologic changes were evaluated. In vitro, IL-6 and TNF-α production by monocytes from the spleen was determined under the stimulation of LPS with VIP, VPAC1-R agonist, or VPAC2-R agonist, and the expression of VPAC1-R and VPAC2-R mRNA in monocytes was examined. Results: VPAC 1-R agonist significantly decreased serum amylase, IL-6, and TNF-α, whereas VPAC2-R agonist markedly increased serum amylase. Histologically, VIP and VPAC1-R agonist attenuated the severity of pancreatitis, although VPAC2-R agonist or secretin showed no significant effect. In vitro, VPAC1-R and VPAC2-R mRNA were obviously expressed in monocytes. Under the stimulation with LPS, VIP presented a biphasic pattern that once decreased IL-6 production from monocytes and then enhanced at high concentration. VPAC1-R agonist reduced IL-6 levels, whereas VPAC2-R agonist increased IL-6 dose-dependently. VPAC1-R agonist reduced TNF-α levels in a dose-dependent manner. Conclusion: VIP attenuated the experimental acute pancreatitis enzymatically and morphologically by inhibiting proinflammatory cytokine production from monocytes mainly through the VPAC1-R.",
author = "Mizuho Kojima and Tetsuhide Ito and takamasa ono and Terumasa Hisano and Hisato Igarashi and Yoshiyuki Arita and Ken Kawabe and Coy, {David H.} and Jensen, {Robert T.} and Hajime Nawata",
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T1 - VIP attenuation of the severity of experimental pancreatitis is due to VPAC1 receptor-mediated inhibition of cytokine production

AU - Kojima, Mizuho

AU - Ito, Tetsuhide

AU - ono, takamasa

AU - Hisano, Terumasa

AU - Igarashi, Hisato

AU - Arita, Yoshiyuki

AU - Kawabe, Ken

AU - Coy, David H.

AU - Jensen, Robert T.

AU - Nawata, Hajime

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Objectives: VIP receptor has been clarified to exist on immune cells, indicating its possible involvement in immunity and inflammatory response. Therefore, we investigated the effects of VIP and selective agonists for 2 subtypes of VIP receptor (VPAC1-R and VPAC2-R agonist) on acute pancreatitis. Methods: Acute pancreatitis was induced in mice by 4 intraperitoneal injections of cerulein and an injection of LPS. VIP, VPAC 1-R agonist, VPAC2-R agonist, or secretin (5 nmol/body) was administered 30 minutes before and after the administration of LPS. Serum amylase and cytokine levels were determined, and histologic changes were evaluated. In vitro, IL-6 and TNF-α production by monocytes from the spleen was determined under the stimulation of LPS with VIP, VPAC1-R agonist, or VPAC2-R agonist, and the expression of VPAC1-R and VPAC2-R mRNA in monocytes was examined. Results: VPAC 1-R agonist significantly decreased serum amylase, IL-6, and TNF-α, whereas VPAC2-R agonist markedly increased serum amylase. Histologically, VIP and VPAC1-R agonist attenuated the severity of pancreatitis, although VPAC2-R agonist or secretin showed no significant effect. In vitro, VPAC1-R and VPAC2-R mRNA were obviously expressed in monocytes. Under the stimulation with LPS, VIP presented a biphasic pattern that once decreased IL-6 production from monocytes and then enhanced at high concentration. VPAC1-R agonist reduced IL-6 levels, whereas VPAC2-R agonist increased IL-6 dose-dependently. VPAC1-R agonist reduced TNF-α levels in a dose-dependent manner. Conclusion: VIP attenuated the experimental acute pancreatitis enzymatically and morphologically by inhibiting proinflammatory cytokine production from monocytes mainly through the VPAC1-R.

AB - Objectives: VIP receptor has been clarified to exist on immune cells, indicating its possible involvement in immunity and inflammatory response. Therefore, we investigated the effects of VIP and selective agonists for 2 subtypes of VIP receptor (VPAC1-R and VPAC2-R agonist) on acute pancreatitis. Methods: Acute pancreatitis was induced in mice by 4 intraperitoneal injections of cerulein and an injection of LPS. VIP, VPAC 1-R agonist, VPAC2-R agonist, or secretin (5 nmol/body) was administered 30 minutes before and after the administration of LPS. Serum amylase and cytokine levels were determined, and histologic changes were evaluated. In vitro, IL-6 and TNF-α production by monocytes from the spleen was determined under the stimulation of LPS with VIP, VPAC1-R agonist, or VPAC2-R agonist, and the expression of VPAC1-R and VPAC2-R mRNA in monocytes was examined. Results: VPAC 1-R agonist significantly decreased serum amylase, IL-6, and TNF-α, whereas VPAC2-R agonist markedly increased serum amylase. Histologically, VIP and VPAC1-R agonist attenuated the severity of pancreatitis, although VPAC2-R agonist or secretin showed no significant effect. In vitro, VPAC1-R and VPAC2-R mRNA were obviously expressed in monocytes. Under the stimulation with LPS, VIP presented a biphasic pattern that once decreased IL-6 production from monocytes and then enhanced at high concentration. VPAC1-R agonist reduced IL-6 levels, whereas VPAC2-R agonist increased IL-6 dose-dependently. VPAC1-R agonist reduced TNF-α levels in a dose-dependent manner. Conclusion: VIP attenuated the experimental acute pancreatitis enzymatically and morphologically by inhibiting proinflammatory cytokine production from monocytes mainly through the VPAC1-R.

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M3 - Article

VL - 30

SP - 62

EP - 70

JO - Pancreas

JF - Pancreas

SN - 0885-3177

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