Laminins are basement membrane (BM) molecules that mediate cell functions such as adhesion, proliferation, migration and differentiation. In the normal small intestine, laminin-5 and laminin-10 are mainly expressed at the base of villus cells. However, in Crohn's disease (CD), a major redistribution of these laminins to the crypt region of the inflamed ileal mucosa has been observed suggesting a possible relation between laminin expression and cytokine and/or growth factor production, which is also altered in CD. The aim of this study was to test the hypothesis that pro-inflammatory cytokines can modulate laminin expression by intestinal epithelial cells. The effect of TNF, IFN, IL-1, IL-6 and TGF was analyzed on the expression of laminins in the normal human intestinal epithelial crypt (HIEC) cell line. When treated with a single cytokine, HIEC cells secreted small amounts of laminin-5 and 10. Only TNF and TGF induced a slight increase in the secretion of these laminins. However, in combination, TNF and IFN synergistically stimulated the secretion of both laminin-5 and 10 in HIEC cells. Transcript analyses suggested that the up-regulation of the two laminins might depend upon distinct mechanisms. Interestingly, the TNF and IFN combination was also found to significantly promote apoptosis. However, the effect of cytokines on the secretion of laminins was maintained even after completely blocking apoptosis by inhibiting caspase activities. These results demonstrate that laminin production is specifically modulated by the pro-inflammatory cytokines TNF and IFN in intestinal epithelial cells under an apoptosis-independent mechanism.