Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro.

Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro. Research Abstract Details 

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Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro. Abstract Text:

Tomoaki Ando,Robert R Langley,Yuping Wang,Paul A Jordan,Alireza Minagar,J Steven Alexander,Merilyn H Jennings,Tomoaki Ando,Robert R Langley,Yuping Wang,Paul A Jordan,Alireza Minagar,J Steven Alexander,Merilyn H Jennings,

BACKGROUND: MAdCAM-1 plays a central role in T-lymphocyte homing to the gut, but its role in chronic liver inflammation remains unknown. Therefore, this study measured MAdCAM-1 expression, regulation, and function in cultured murine hepatic endothelial cells. METHODS: Cultures of hepatic endothelial cells (HEC) were prepared from mice expressing a temperature-sensitive SV40 large T antigen (H-2Kb-tsA58) under the control of an IFN-gamma promoter. Time and dose dependent expression of MAdCAM-1 in response to TNF-alpha, IL-1 beta and IFN-gamma was studied by immunoblotting. Lymphocyte adhesion was studied using alpha 4 beta 7 integrin expressing lymphocytes (TK-1) +/- anti-MAdCAM-1 mAb. RESULTS: TNF-alpha induced MAdCAM-1 dose-and time-dependently with maximum expression at 20 ng/ml and at 48 hours. IL-1 beta also induced MAdCAM-1 to a lesser extent compared to TNF-alpha; IFN-gamma did not induce MAdCAM-1. TNF-alpha significantly increased lymphocyte-endothelial adhesion (P < 0.01), which was reversed by anti-MAdCAM-1 antibody. MAdCAM-1 expression was also reduced by N-acetylcysteine and by two NO donors (SperNO, DETANO) suggesting that hepatic endothelial MAdCAM-1 is oxidant and NO regulated. CONCLUSION: MAdCAM-1 is a major determinant of leukocyte recruitment in chronic inflammation and is expressed by HEC in response to IL-1 beta and TNF-alpha. This system may provide a useful model for studying inflammatory mechanisms in liver disease and help determine if controlled MAdCAM-1 expression might influence inflammation in liver disease.

Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro. Publishing Authors By Initials

T Ando,RR Langley,Y Wang,PA Jordan,A Minagar,JS Alexander,MH Jennings,T Ando,RR Langley,Y Wang,PA Jordan,A Minagar,JS Alexander,MH Jennings,

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Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: BMC physiology

VOLUME: 7

Page Numbers: 10

Journal Abbreviation: BMC Physiol.

ISSN: 1472-6793

DAY: 14

MONTH: 09

YEAR: 2007

Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro. Information

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LANGUAGE: eng

NlmUniqueID: 101088687

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Grant and Affiliation Information for Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro.

AFFILIATION: Nagoya City Medical University, 1-Kawasumi-Mizuho, Nagoya, 467-8601, Japan. andytomo@hotmail.com

Country: England

AGENCY: United States NIDDK

GRANT: DK43785

ACRONYM: DK

MEDLINETA: BMC Physiol

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