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Interleukin‐4 inhibits prostaglandin G/H synthase‐2 and cytosolic phospholipase A 2 induction in neonatal mouse parietal bone cultures
Author(s) -
Kawaguchi Hiroshi,
Nemoto Ken,
Raisz Lawrence G.,
Harrison John R.,
Voznesensky Olga S.,
Alander Cynthia B.,
Pilbeam Carol C.
Publication year - 1996
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650110309
Subject(s) - endocrinology , medicine , cycloheximide , arachidonic acid , phospholipase a2 , prostaglandin e2 , prostaglandin , parathyroid hormone , biology , messenger rna , chemistry , enzyme , microbiology and biotechnology , calcium , protein biosynthesis , biochemistry , gene
We have shown previously that prostaglandin (PG) production in 7‐day‐old neonatal mouse calvarial cultures is regulated largely by changes in prostaglandin G/H synthase‐2 (PGHS‐2) expression and to a lesser extent by changes in arachidonic acid (AA) release. In this study, we examined the effects of interleukin‐4 (IL‐4), and its interactions with other cytokines and with parathyroid hormone (PTH), on mRNA levels of PGHS‐2, PGHS‐1, and cytosolic phospholipase A 2 (cPLA 2 ) and on medium protaglandin E 2 (PGE 2 ) levels in calvarial cultures. IL‐1 and tumor necrosis factor‐α (TNF‐α), both at 1–100 ng/ml, and PTH at 0.1‐10 nM increased PGHS‐2 and cPLA 2 mRNA and medium PGE 2 levels dose‐dependently after 4 h of treatment. IL‐6 and IL‐11 at 1–100 ng/ml did not affect mRNA or PGE 2 levels. IL‐4 at 1–100 ng/ml decreased PGHS‐2 and cPLA 2 mRNA and PGE 2 levels in control as well as IL‐1, TNF‐α, and PTH‐stimulated cultures. The inhibition of PGHS‐2 and cPLA 2 mRNA expression by IL‐4 (10 ng/ml) was present at 1 h, reached a maximum at 4 h, and persisted for 24 h. The effects were maintained in the presence of cycloheximide. IL‐4 also decreased PGHS‐2 protein levels in control and IL‐1‐stimulated cultures. PGHS‐1 mRNA levels were not stimulated by any of the factors studied nor inhibited by IL‐4. IL‐4 partially inhibited control and PTH‐stimulated 45 Ca release from prelabeled mouse calvariae at 4 days. However, neither the inhibition of resorption by IL‐4 nor the stimulation by IL‐1 and PTH were altered by indomethacin (1 μM). We conclude that (1) IL‐1, TNF‐α, and PTH, but not IL‐6 nor IL‐11, can increase the expression of PGHS‐2, cPLA 2 , and PGE 2 production in cultured mouse calvariae; (2) IL‐4 inhibits PGE 2 production in both control and stimulated calvarial cultures by inhibiting PGHS‐2 and cPLA 2 ; and (3) IL‐4 has an inhibitory effect on bone resorption which is independent of PG production.