Disruption of the integrity of human peritoneal mesothelium by interleukin-1β and tumor necrosis factor-α

Inflammatory and neoplastic disease processes of the abdominal cavity are frequently associated with disruption of the integrity of the peritoneal mesothelium. In the present study, we analyzed the effects of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the morphology and expression of adhesion molecules of human peritoneal mesothelial cells (HPMC). Treatment of HPMC with IL-1β and TNF-α resulted in a time- and dose-dependent alteration of the normal cobblestone morphology of the mesothelium with loss of polarization, cellular retraction and exposure of the submesothelial matrix. The effect was already observable after 6 h of treatment and was most pronounced at a dose of 10 ng/ml of IL-1β or TNF-α. These morphological alterations were associated with a significant rearrangement of the expression of mesothelial adhesion molecules as detected by flow cytometry. IL-1β and TNF-α both led to a loss of the expression of the hemidesmosomal integrin subunits α6 (P<0.01 and P<0.001) and β4 (P<0.01) and an increased expression of the integrin subunit α5 (P<0.001 and P<0.01). IL-1β furthermore upregulated the expression of the integrin subunits α1, α2 and the adhesion molecule CD44 while the latter was downregulated by TNF-α. Our data indicate that IL-1β and TNF-α may significantly affect disease processes of the abdominal cavity by their potential to disrupt the mesothelial basal cell-matrix adhesion and, thus, the integrity of the peritoneal mesothelial cell lining.