Treatment with anti-transforming growth factor beta antibodies influences an altered pattern of cytokines gene expression in injured rat liver.
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.
Institute of Molecular Biology in Medicine, CUCS, University of Guadalajara, Apdo. Postal 2-500, 44281 Guadalajara, Jal, Mexico.
V
V
Delgado-Rizo
A
A
Salazar
A
A
Panduro
J
J
Armendáriz-Borunda
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008115:Liver Regeneration / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000276:immunology
D000906:Antibodies; D016207:Cytokines; D016212:Transforming Growth Factor beta