Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion In VitroReportar como inadecuado




Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion In Vitro - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Physiology

, 7:10

First Online: 14 September 2007Received: 17 August 2006Accepted: 14 September 2007

Abstract

BackgroundMAdCAM-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.

MethodsCultures of hepatic endothelial cells HEC were prepared from mice expressing a temperature-sensitive SV40 large T antigen H-2K-tsA58 under the control of an IFN-γ promoter. Time and dose dependent expression of MAdCAM-1 in response to TNF-α, IL-1β and IFN-γ was studied by immunoblotting. Lymphocyte adhesion was studied using α4β7integrin expressing lymphocytes TK-1 +- anti-MAdCAM-1 mAb.

ResultsTNF-α induced MAdCAM-1 dose-and time-dependently with maximum expression at 20 ng-ml and at 48 hours. IL-1β also induced MAdCAM-1 to a lesser extent compared to TNF-α; IFN-γ did not induce MAdCAM-1. TNF-α 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.

ConclusionMAdCAM-1 is a major determinant of leukocyte recruitment in chronic inflammation and is expressed by HEC in response to IL-1β and TNF-α. 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.

List of abbreviationsHEChepatic endothelial cells

MAdCAM-1Mucosal addressin cell adhesion molecule-1

ICAM-1intercellular adhesion molecule-1

ICAM-1intercellular adhesion molecule-2

VCAM-1vascular cell adhesion molecule-1 VCAM-1 PSC, ECAMs, endothelial cell adhesion molecules

PSCprimary sclerosing cholangitis

PBCprimary biliary cirrhosis

NACN-acetyl cysteine

I-Rischemia and reperfusion

TKtyrosine kinase

AcLDLacetylated low density lipoprotein AcLDL

ROSreactive oxygen species

e-NOSendothelial nitric oxide synthase e-NOS

iNOSinducible nitric oxide synthase

ONOOperoxynitrite

IBDinflammatory bowel disease

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6793-7-10 contains supplementary material, which is available to authorized users.

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Autor: Tomoaki Ando - Robert R Langley - Yuping Wang - Paul A Jordan - Alireza Minagar - J Steven Alexander - Merilyn H Jennin

Fuente: https://link.springer.com/



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