Interleukin-6 (IL-6) is a pro-inflammatory cytokine that plays an important role 
in the pathogenesis of inflammatory bowel disease. TGF-beta, a multifunctional 
cytokine, is a potent negative regulator of mucosal inflammation in the 
intestine. The aim of the present study is to determine possible cross-talk 
between IL-6 and TGF-beta signaling pathways. Model intestinal epithelial cell 
lines, Caco2-BBE were used. We show that TGF-beta receptor Type II is 
predominantly present in the basolateral membrane of intestinal epithelial 
cells. TGF-beta1 induces a time-dependent phosphorylation of Smad2 and 
co-immunoprecipitation of SMAD-2 with Smad-4 and its subsequently translocation 
to the nucleus. We show that pretreatment of cells with TGF-beta1 is associated 
with a down-regulation of IL-6 induced tyrosine phosphorylation of STAT1 and 
STAT3 and suppression of ICAM-1 expression. Furthermore, TGF-beta1 pretreatment 
resulted in a significant inhibition of IL-6 induced ICAM-1 promoter activity. 
TGF-beta mediated inhibition of IL-6 induced ICAM-1 expression was reversed by 
transfection with dominant negative Smad2 constructs. In conclusion, we show 
that: 1) TGF-beta receptor Type II is predominantly located on basolateral 
membrane and receptor stimulation activates Smad pathway; 2) TGF-beta1 
down-regulates IL-6-induced tyrosine phoshorylation of STAT1 and STAT3 and 
ICAM-1 expression; and 3) Smad2 is required for the down-regulation of IL-6 
signaling by TGF-beta. Collectively, our data demonstrate a cross-talk between 
TGF-beta and IL-6, and TGF-beta may play a role in the negative regulation of 
IL-6 signaling in intestinal epithelial cells.