Interleukin 1 alpha acts as an autocrine growth stimulator for human gastric carcinoma cells

The expression and effect of interleukin 1 alpha (IL-1 alpha) were examined in human gastric carcinoma cell lines to determine if IL-1 alpha acts as a growth stimulator for these cells. Six of 8 gastric carcinoma cell lines expressed IL-1 alpha mRNA at various levels. Among them, TMK-1 and MKN-7 cells secreted IL-1 alpha into the culture fluid, in an especially large amount by MKN-7 cells. Scatchard plot analysis of IL-1 alpha binding revealed that TMK-1 cells had only one type of high-affinity receptors, whereas MKN-7 cells had high- and low-affinity receptors. Cell growth and DNA synthesis of TMK-1 and MKN-7 cells were stimulated by IL-1 alpha, and those of MKN-7 were inhibited by addition of anti-IL-1 alpha antibody or IL-1 receptor antagonist. The expression of IL-1 alpha mRNA by these cell lines was induced by either IL-1 alpha, epidermal growth factor, or transforming growth factor alpha. On the other hand, IL-1 alpha increased the mRNA expression for transforming growth factor alpha and epidermal growth factor receptor. These findings indicate that IL-1 alpha is an autocrine growth stimulator for gastric carcinoma cells and the interaction with epidermal growth factor/transforming growth factor alpha/receptor system should be involved in the growth modulation by IL-1 alpha.