title: Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial lipopolysaccharide that acts in synergy with c-kit ligand and Fc epsilon receptor I crosslinking in cultured mast cells.
abstract: Emerging evidence has suggested the pivotal role of mast cells in a host defense against bacterial infection. In this paper, we report that bacterial lipopolysaccharide (LPS) is a potent enhancer of the cytokine- and IgE-dependent delayed responses of IL-3-dependent mouse bone marrow-derived cultured mast cells (BMMC). LPS, although showing minimal effects, significantly augmented the c-kit ligand (KL)- or IgE-dependent expression of cyclooxygenase (COX)-2 and the attendant delayed PGD2 generation, with IL-10 and IL-4 acting as potentiating and inhibitory cytokines, respectively. The COX-2-inducing activity of LPS was mimicked by exogenous IL-1 beta. Assessment of endogenous cytokine induction 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, depended 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 and 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyonsan, Korea.
authors.forename: T C
authors.initials: TC
authors.lastname: Moon
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: M D
authors.initials: MD
authors.lastname: Ashraf
authors.forename: I
authors.initials: I
authors.lastname: Kudo
authors.forename: H W
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D004357:Drug Synergism; D004790:Enzyme Induction / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D017455:Receptors, IgE / Q000378:metabolism* / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000276:immunology; D013997:Time Factors
chemical_list: D016207:Cytokines; D007106:Immune Sera; D007527:Isoenzymes; D008024:Ligands; D008070:Lipopolysaccharides; D017455:Receptors, IgE; D017472:Receptors, Interleukin-1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019009:Proto-Oncogene Proteins c-kit; D015230:Prostaglandin D2