Co-culture of human monocytes and thyrocytes in bicameral chamber: Monocyte-derived IL-1 alpha impairs the thyroid epithelial barrier

Pro-inflammatory cytokines are important mediators in tissue responses to a wide range of endogenous (e.g. autoantigens) and exogenous (e.g. infection s, wounds, biomaterials) stimuli. The complex interactions taking place bet ween different cell types in such processes are difficult to examine in viv o. Here we studied the effect of human monocytes on thyroid epithelial cell s co-cultured in bicameral chambers. Freshly isolated monocytes (1 x 10(6)/ ml) added to the basal compartment reduced the transepithelial resistance ( from 300-600 to <100 Omega . cm(2)) and caused a disruption of the tight ju nctions in apically grown thyrocyte monolayers after co-culture for 24 h, T he barrier function was further attenuated by monocytes exposed to lipopoly saccharide (10 mu g/ml) or polystyrene microspheres (size: 3 mu m; 1 x 10(7 )/ml), Loss of transepithelial resistance was accompanied by release of int erleukin la (maximally 550 pg/ml) from the monocytes, Conversely, the resis tance remained high when co-cultures were simultaneously incubated with neu tralizing anti-human interleukin 1 alpha antibodies. The results show that the integrity of cultured thyroid epithelium is impaired by monocytes witho ut requirement of direct cell-to-cell contact. This action, mediated by int erleukin-la, suggests a mechanism by which hidden (lumenal) autoantigens mi ght be exposed to interstitial antigen-presenting cells in autoimmune thyro id disease. In perspective, the model provides a tool in which humoral and cell-cell dependent processes generated by bioactive agents and particulate materials, for instance, during the healing and repair of tissue around bi omaterials and hybrid implants, can be selectively examined. (C) 2000 Acade mic Press.