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The view that the two isoforms of prostaglandin-endoperoxide synthase (cyclooxygenase), PGHS-1 and PGHS-2, mediate physiologic and inflammatory processes, respectively, implies separate pathways of arachidonic acid metabolism with different benefits to the host. Functional segregation of these steps in endogenous arachidonic acid metabolism in a single cell in response to different stimuli is now demonstrated. When mouse bone marrow-derived mast cells developed in interleukin-3 (IL-3)-containing medium were cultured with c-kit ligand in combination with IL-10 and IL-1 beta, transient expression of PGHS-2 mRNA and protein occurred in a dose- and time-dependent fashion, accompanied by substantial release of prostaglandin D2 (PGD2) into the culture medium from 2 to 10 h. In contrast, induction of PGHS-2 did not mediate an increase in PGD2 generation in response to stimulation with IgE and antigen. After a longer period of culture, from 24 to 48 h, the expression of PGHS-1 increased, as did the increase in IgE/antigen-dependent generation of PGD2. Dexamethasone, which inhibited the induction of PGHS-2 but not PGHS-1, and a PGHS-2-selective inhibitor suppressed cytokine-induced PGD2 generation but not IgE-dependent PGD2 generation. Thus, at a time when both PGHS-1 and PGHS-2 are present in bone marrow-derived mast cells, they function independently by coupling to different stimulus-initiated pathways to PGD2 generation from endogenously derived arachidonic acid.
M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
October 1996,
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M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
February 2002,
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M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
July 1995,
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M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
February 1994,
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M Murakami, and
R Matsumoto, and
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J P Arm
November 1988,
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M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
February 1997,
The Journal of biological chemistry,
M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
May 1995,
The Journal of biological chemistry,
M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
April 2001,
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M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
June 1995,
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M Murakami, and
R Matsumoto, and
K F Austen, and
J P Arm
April 1994,
Annals of the New York Academy of Sciences,
