REGULATION OF CYCLOOXYGENASE-2 AND ENDOGENOUS CYTOKINE EXPRESSION BY BACTERIAL LIPOPOLYSACCHARIDE THAT ACTS IN SYNERGY WITH C-KIT LIGAND AND FC-EPSILON RECEPTOR-I CROSS-LINKING IN CULTURED MAST-CELLS

Emerging evidence has suggested the pivotal role of mast cells in a ho st defense against bacterial infection. In this paper, we report that bacterial lipopolysaccharide (LPS) is a potent enhancer of the cytokin e-and IgE-dependent delayed responses of IL-3-dependent mouse bone mar row-derived cultured mast cells (BMMC). LPS, although showing minimal effects, significantly augmented the c-kit ligand (KL)- or IgE-depende nt expression of cyclooxygenase (COX)-2 and the attendant delayed PGD( 2) generation, with IL-10 and IL-4 acting as potentiating and inhibito ry cytokines, respectively. The COX-2-inducing activity of LPS was mim icked by exogenous IL-1 beta. Assessment of endogenous cytokine induct ion revealed that IL-1 beta expression was stimulated by either LPS or exogenous IL-1 beta. IL-6 expression occurred in parallel with COX-2 expression. IL-10 expression, which lagged behind COX-2 expression, de pended on exogenous IL-10, but not on LPS and IL-1 beta. Thus, LPS and IL-1 beta exhibited similar biological activities in terms of COX-2 a nd endogenous cytokine expression. However, adding an antibody against the type I IL-1 receptor to BMMC, which abrogated the effects of IL-1 beta, failed to neutralize the effects of LPS. These results suggest that LPS activates BMMC through the signal transduction pathway shared with exogenous IL-1 beta, rather than exerting its action indirectly via the production of endogenous IL-1 beta. (C) 1998 Academic Press.