Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host diseaseReport as inadecuate




Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 8:R123

First Online: 19 July 2006Received: 17 April 2006Revised: 06 July 2006Accepted: 14 July 2006

Abstract

Chronic graft-versus-host disease GVHD induced in C57BL-6 × DBA-2 F1 BDF1 mice by the injection of DBA-2 mouse spleen cells represents histopathological changes associated with systemic lupus erythematosus SLE, primary biliary cirrhosis PBC and Sjogren-s syndrome SS, as indicated by glomerulonephritis, lymphocyte infiltration into the periportal area of the liver and salivary glands. We determined the therapeutic effect of hepatocyte growth factor HGF gene transfection on lupus using this chronic GVHD model. Chronic GVHD mice were injected in the gluteal muscle with either HVJ liposomes containing 8 μg of the human HGF expression vector HGF-HVJ liposomes or mock vector untreated control. Gene transfer was repeated at 2-week intervals during 12 weeks. HGF gene transfection effectively prevented the proteinuria and histopathological changes associated with glomerulonephritis. While liver and salivary gland sections from untreated GVHD mice showed prominent PBC- and SS-like changes, HGF gene transfection reduced these histopathological changes. HGF gene transfection greatly reduced the number of splenic B cells, host B cell major histocompatibility complex class II expression, and serum levels of IgG and anti-DNA antibodies. IL-4 mRNA expression in the spleen, liver, and kidneys was significantly decreased by HGF gene transfection. CD28 expression on DBA-2 CD4+ T cells was decreased by the addition of recombinant HGF in vitro. Furthermore, IL-4 production by DBA-2 CD4+ T cells stimulated by irradiated BDF1 dendritic cells was significantly inhibited by the addition of recombinant HGF in vitro. These results suggest that HGF gene transfection inhibited T helper 2 immune responses and reduced lupus nephritis, autoimmune sialoadenitis, and cholangitis in chronic GVHD mice. HGF may represent a novel strategy for the treatment of SLE, SS and PBC.

AbbreviationsCTLcytotoxic T lymphocyte

DCdendritic cell

ELISAenzyme-linked immunosorbent assay

E-Teffector target

FITCfluorescein isothiocyanate

GVHDgraft-versus-host disease

HGFhepatocyte growth factor

HVJhemagglutinating virus of Japan

IFNnterferon

ILinterleukin

mAbmonoclonal antibodies

MHCmajor histocompatibility complex

MLRmixed lymphocyte reaction

PBSphosphate-buffered saline

RT-PCRreverse transcribed PCR

SDstandard deviation

ThT helper.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2012 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Author: Takanori Kuroiwa - Tsuyoshi Iwasaki - Takehito Imado - Masahiro Sekiguchi - Jiro Fujimoto - Hajime Sano

Source: https://link.springer.com/







Related documents