Pro-inflammatory cytokines are important mediators in tissue responses to a wide range of endogenous (e.g. autoantigens) and exogenous (e.g. infections, wounds, biomaterials) stimuli. The complex interactions taking place between different cell types in such processes are difficult to examine in vivo. Here we studied the effect of human monocytes on thyroid epithelial cells co-cultured in bicameral chambers. Freshly isolated monocytes (1x10(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 junctions in apically grown thyrocyte monolayers after co-culture for 24 h. The barrier function was further attenuated by monocytes exposed to lipopolysaccharide (10 microg/ml) or polystyrene microspheres (size: 3 microm; 1x10(7)/ml). Loss of transepithelial resistance was accompanied by release of interleukin 1alpha (maximally 550 pg/ml) from the monocytes. Conversely, the resistance remained high when co-cultures were simultaneously incubated with neutralizing anti-human interleukin 1alpha antibodies. The results show that the integrity of cultured thyroid epithelium is impaired by monocytes without requirement of direct cell-to-cell contact. This action, mediated by interleukin-1alpha, suggests a mechanism by which hidden (lumenal) autoantigens might be exposed to interstitial antigen-presenting cells in autoimmune thyroid 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 biomaterials and hybrid implants, can be selectively examined.
Copyright 2000 Academic Press.