PLEURAL MESOTHELIAL CELL RESPONSE TO INFLAMMATION - TUMOR NECROSIS FACTOR-INDUCED MITOGENESIS AND COLLAGEN-SYNTHESIS

This study examined the effects of tumor necrosis factor-alpha on pleu ral mesothelial cell proliferation and collagen synthesis, functions w hich may be important in the response of the pleura to injury. Tumor n ecrosis factor-alpha caused a significant increase in proliferation an d collagen production by rat pleural mesothelial cells in vitro. Proli feration increased in a time- and dose-dependent manner, resulting in an approximate twofold increase in the uptake of [H-3]thymidine relati ve to control. The uptake of [H-H]proline into collagenase-sensitive p rotein increased in a dose-dependent manner for concentrations of tumo r necrosis factor-alpha greater-than-or-equal-to 1.0 ng/ml. The increa ses in collagen production were associated with increased steady-state levels of alpha1(I)-procollagen mRNA. These results suggest that tumo r necrosis factor-alpha may have a significant effect on pleural mesot helial cell function in vivo in the setting of inflammation. Increases in pleural mesothelial cell proliferation and collagen synthesis in r esponse to inflammatory mediators, like tumor necrosis factor-alpha, m ay be important in healing the pleura after injury by a variety of dis ease processes.