Modulation of transglutaminase 2 expression in the human intestinal mucosa.

M. BAYARDO,; Y. ALLEGRETTI,; M. RUMBO,; F. G. CHIRDO;

Rio de Janeiro, Brasil

Congreso; Congress of the International Union of Immunology Societies; 2007

nternational Union of Immunology Societies

Transglutaminase 2 (TG2) participates in diverse biological processes such as wound healing,signalling, cell differentiation and apoptosis. TG2 is upregulated in the intestinal mucosa inactive coeliac patients being involved in its pathogenic mechanism in which Th1 cytokines(mainly  IFN) are the hallmark. Stimuli modulating TG2 expression in the epithelium are not yetfully elucidated.Caco-2 and HT-29 cells, human intestinal epithelial cell lines commonly used as a model forenterocytes, were incubated for 24 h with different cytokines. The total RNA was collected andTG2 mRNA levels were determined by quantitative PCR. IFN produced 4,5 fold increase of TG2 expression in both Caco-2 and HT-29 cells. TNF produced 2,6 fold increase in HT-29 and lower response in Caco-2 cells. A synergyupregulation was observed when Caco-2 cells were incubated with TNF  and  IFN.In HT-29 cells, IL-1 produced 2,8 fold increase, while a slight increase in TG2 mRNA levels wasobserved in Caco-2 cells. IL-6 and TGFb, tested in HT-29 cells, produced 2,5 fold increase. Inall cases analysed, HT-29 showed a higher response than Caco-2 cells.Western blot analysis failed to detect relevant differences in TG2 content among treatments.We cloned the TG2 promoter which showed several putative binding sites for different nuclearfactors such as SP1, AP-1, NFkB, which may explain the complex regulatory pathways involvedin TG2 expression.In conclusion, TG2 was strongly induced in Caco-2 and HT-29 cells by  IFN, cytokine whichmay act as the main TG2 inducer in the damaged intestinal tissue.