p38 MAP kinase regulates TNF alpha-, IL-1 alpha- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells

Background RANTES and granulocyte macrophage-colony stimulating factor (GM- CSF) play an important role in the production of allergic inflammation of t he airway through their chemotactic activity for eosinophils. Recent studie s have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase i n RANTES and GM-CSF production in human bronchial epithelial cells (BECs) h as not yet been determined. Objective In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kina se activation in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alp ha and platelet-activating factor (PAF)stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs. Results The results showed that TNF alpha. IL-1 alpha and PAF induced serin e phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SE 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF productio n by TNF alpha-, IL-1 alpha- or PAF-stimulated human BECs, Conclusions These results indicate that p38 MAP kinase plays an important r ole in TNF alpha- IL-1 alpha- or PAF-activated signalling pathway which reg ulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.