Treatment with anti-transforming growth factor beta antibodies influences an altered pattern of cytokines gene expression in injured rat liver

Biochim Biophys Acta. 1998 Oct 23;1442(1):20-7. doi: 10.1016/s0167-4781(98)00111-0.

Abstract

The role of transforming growth factor beta1 (TGF-beta1) in mediating hepatic inflammation and regeneration after acute liver injury is beginning to be elucidated, yet its in vivo effect on the gene expression of the major pro-inflammatory and anti-inflammatory cytokines produced during that process is unknown. Our previous experiments demonstrated that anti-TGF-beta-treated animals presented profound histological changes as compared with control animals. Therefore, our hypothesis was that by blocking in vivo TGF-beta1 action, with polyclonal anti-TGF-beta antibodies, we could monitor by RT-PCR significative alterations on the gene expression of IL-1beta, IL-6, TGF-beta, TNF-alpha, IL-4 and IL-10 in liver-regenerated rats after administration of a single CCl4 dosing. Accordingly, we here report a completely different pattern of cytokines gene expression amidst those groups of rats. Pro-inflammatory cytokines gene expression in control animals showed a clear-cut pattern peaking at 1-2 days postinjury and declining thereafter. Interestingly, IL-6 was present in the control animals only between 12 and 24 h after CCl4 dosing. In the experimental animals, TGF-beta1 was mainly increased at 4 and 6 days, while IL-6 mRNA was completely absent. IL-1beta mRNA expression was also altered in the experimental rats, albeit TNF-alpha was nearly unaffected. IL-4 was fully absent in control rats, but remarkably expressed in experimental animals throughout the study. IL-10 was also more expressed in experimental animals.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Gene Expression Regulation / drug effects
  • Liver / metabolism*
  • Liver / pathology*
  • Liver Regeneration / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / immunology

Substances

  • Antibodies
  • Cytokines
  • Transforming Growth Factor beta