Autocrine mechanism of GM-CSF production in human fibroblasts

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Prior study by us found that expression of GM-CSF mRNA in human embryonic lung fibroblasts W138 is regulated through an autocrine stimulation by IL-1 production. In the present study, we showed that expression of manganese superoxide dismutase (MnSOD) gene is also regulated by an autocrine mechanism in these cells ; treatment of cells with either anti-IL-1 alpha or beta antibody reduced the constitutive expession of MnSOD mRNA.These results indicate that the autocrine stimulation may be one of the important mechanisms in expression of genes as well as GM-CSF.To further investigate the role of IL-1 in induction of GM-CSF or MnSOD,cells were irradiated in the presence of anti-IL-1 antibody. Irradiation increased the levels of GM-CSF and MnSOD mRNAs in a dose- and time-dependent fashion. Treatment with anti-IL-1 antibody blocked the induction of these mRNAs in these cells and exogenously added-IL-1 increased the levels of these mRNAs. Similar results were also obtained in the experiment using human monocytic cells THP-1. Irradiation increased the production of tumor necrosis factor (TNF) in a dose dependent manner. Irradiation induced the expression of MnSOD mRNA and treatment of these cells with anti-TNF antibody inhibited the induction of MnSOD mRNA by irradiation. Furthermore, we also found that irradiation increased expression of WAF1/CIP1, p21, through the production of TNF in human myeloblastic cells KG1. Our present studies indicate an autocrine or paracrine mechanism (s) may play an important role in expression of genes in various cells.