Cross-linking of the high-affinity IgE receptor induces the expression of cyclo-oxygenase 2 and attendant prostaglandin generation requiring interleukin 10 and interleukin 1 beta in mouse cultured mast cells.
When mouse bone marrow-derived mast cells (BMMC) developed in interleukin (IL)-3 were activated with IgE and antigen (IgE/antigen) in the presence of both IL-10 and IL-1 beta, two sequential phases of prostaglandin (PG)D2 generation were elicited, in which the first phase occurred by 1 h and the second phase from 2 to 10 h. The delayed phase of PGD2 generation was accompanied by a marked induction of cyclo-oxygenase (COX)-2 mRNA, which reached a peak at 1-2 h, followed by that of its protein from 2-10 h, with a peak at 5 h. The immediate phase of PGD2 generation was completely abrogated by the irreversible inhibition of pre-existing COX-1 by aspirin pretreatment, whereas the delayed phase of PGD2 generation was almost undetectable in the presence of the COX-2 inhibitor NS-398. A detailed analysis of the individual effects of IgE/antigen, IL-10 and IL-1 beta on COX-2 expression revealed that IgE/antigen and IL-10 each initiated and stabilized COX-2 mRNA expression, leading to an increase in the expression of its protein. Conversely, IL-1 beta stabilized the COX-2 protein without affecting its mRNA level. The induction of COX-2 by IgE/antigen with IL-10 and IL-1 beta preceded the induction of transcripts for endogenous cytokines such as IL-6, IL-1 beta and IL-10. The inhibition of PGD2 generation by indomethacin did not affect the induction of COX-2 or these cytokines. Thus the two major delayed-phase responses of BMMC after IgE-dependent activation, namely COX-2-dependent PGD2 generation and cytokine production, are regulated independently.
Ashraf
M
M
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Murakami
M
M
Kudo
I
I
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D051546:Cyclooxygenase 2; D005786:Gene Expression Regulation / Q000235:genetics; D007073:Immunoglobulin E / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015230:Prostaglandin D2 / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D019089:Stem Cell Factor / Q000494:pharmacology
D000941:Antigens; D007375:Interleukin-1; D007527:Isoenzymes; D017455:Receptors, IgE; D019089:Stem Cell Factor; D016753:Interleukin-10; D007073:Immunoglobulin E; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2