Regulatory Activity of Endogenous and Exogenous Transforming Growth Factorβin Experimental Intestinal Immunopathology
作者:
MowatA. McI.,
GarsideP.,
FittonL. A.,
HigleyH. R.,
CarlinoJ. A.,
期刊:
Growth Factors
(Taylor Available online 1996)
卷期:
Volume 13,
issue 1-2
页码: 75-85
ISSN:0897-7194
年代: 1996
DOI:10.3109/08977199609034568
出版商: Taylor&Francis
关键词: Craft-versus-host disease;intestinal pathology;transforming growth factorβ;immunotherapy
数据来源: Taylor
摘要:
AbstractAcute graft-versus-host disease (GvHD) is an inflammatory disorder associated with generalised damage to epithelial tissues, including the gastrointestinal tract. There is increasing evidence that this pathology is due to the effects of cytokines on epithelial cell proliferation and differentiation. However, it is unclear whether factors derived from immune cells act directly on epithelial cells or via other mediators whose principal role is to regulate cell growth under normal or diseased conditions. We show here that the increased crypt cell turnover and lymphocytic infiltration which occurs in the jejunum of mice with graft-versus-host reaction (GvHR) is accompanied by decreased enterocyte expression of transforming growth factorβ2. Administration of exogenous TGFβinhibits the crypt hyperplasia of GvHR and reduces systemic manifestations of GvHR such as increased splenic natural killer (NK) cell activity. In parallel, neutralisation of endogenous TGFβby monoclonal antibody exacerbates both the proliferative and inflammatory components of intestinal and systemic GvHR. Thus, the immune system may induce epithelial pathology at least in part by altering the production of endogenous TGFβ. This cytokine may therefore prove a useful focus for therapeutic intervention in immunopathologies such as GvHD.
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