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-1β, 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-exisiting 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-1β 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-1β stabilized the COX-2 protein without affecting its mRNA level. The induction of COX-2 by IgE/antigen with IL-10 and IL-1β preceded the induction of transcripts for endogenous cytokines such as IL-6, IL-1β 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.
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December 1996
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Research Article|
December 15 1996
Cross-linking of the high-affinity IgE receptor induces the expression of cyclo-oxygenase 2 and attendant prostaglandin generation requiring interleukin 10 and interleukin 1β in mouse cultured mast cells
Musharraf ASHRAF;
Musharraf ASHRAF
1Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan
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Makoto MURAKAMI;
Makoto MURAKAMI
1Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan
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Ichiro KUDO
Ichiro KUDO
*
1Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan
*To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
July 03 1996
Revision Received:
August 27 1996
Accepted:
August 29 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 320 (3): 965–973.
Article history
Received:
July 03 1996
Revision Received:
August 27 1996
Accepted:
August 29 1996
Citation
Musharraf ASHRAF, Makoto MURAKAMI, Ichiro KUDO; Cross-linking of the high-affinity IgE receptor induces the expression of cyclo-oxygenase 2 and attendant prostaglandin generation requiring interleukin 10 and interleukin 1β in mouse cultured mast cells. Biochem J 15 December 1996; 320 (3): 965–973. doi: https://doi.org/10.1042/bj3200965
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