MITOGENIC RESPONSE OF RAT LUNG AND TRACHEAL EPITHELIAL-CELLS IN MONOLAYER PRIMARY CULTURES - MODULATION OF TNF-ALPHA EXPRESSION

Epithelial cells isolated from rat lung and trachea were grown on mono layers and their response to a number of hormones and growth factors w ere studied. Maximum proliferative response in serum containing media was observed when insulin, cholera toxin and cortisol were present tog ether. However, these additives when present independently showed a ma rginal response. The synergism, due to these factors in promoting grow th was seen very early in culture (day 4) as shown by thymidine labell ing studies. On examining the indices of early mitogenesis, such as th e expression of c-myc, our data suggests that these factors stimulate the expression of c-myc within 4h. With respect to expression of TNF-a lpha mRNA, this study suggests a possible modulation of TNF-alpha expr ession in response to these mitogens that stimulate proliferation maxi mally. Whether this expression of TNF-alpha by these epithelial cells is due to a maximal proliferative stimulus and/or is an early step in the cascade of intracellular signalling events is to be investigated i n detail.