In vitro effects of cAMP-elevating agents and glucocorticoid either alone or in combination on the production of nitric oxide, interleukin-12 and interleukin-10 in IFN-gamma- and LPS-activated mouse peritoneal macrophages
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
12630324
DOI
10.1007/bf02818676
Knihovny.cz E-zdroje
- MeSH
- aktivace makrofágů účinky léků fyziologie MeSH
- AMP cyklický metabolismus MeSH
- antiflogistika farmakologie MeSH
- dexamethason farmakologie MeSH
- dibutyryl cyklický AMP farmakologie MeSH
- hybridizace nukleových kyselin MeSH
- interferon gama farmakologie MeSH
- interleukin-10 biosyntéza MeSH
- interleukin-12 biosyntéza MeSH
- lipopolysacharidy farmakologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- northern blotting MeSH
- oxid dusnatý biosyntéza MeSH
- peritoneální makrofágy účinky léků enzymologie metabolismus MeSH
- RNA chemie genetika MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého genetika metabolismus MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- AMP cyklický MeSH
- antiflogistika MeSH
- dexamethason MeSH
- dibutyryl cyklický AMP MeSH
- interferon gama MeSH
- interleukin-10 MeSH
- interleukin-12 MeSH
- lipopolysacharidy MeSH
- Nos2 protein, mouse MeSH Prohlížeč
- oxid dusnatý MeSH
- RNA MeSH
- synthasa oxidu dusnatého, typ II MeSH
- synthasa oxidu dusnatého MeSH
The effects of cAMP-elevating agents, N6-2'-O-dibutyryl cAMP (Bu2cAMP), and glucocorticoid (dexamethasone) on the production of inflammatory mediators--nitric oxide and interleukin-12 (IL-12) and anti-inflammatory mediator interleukin-10 (IL-10) were demonstrated in murine peritoneal macrophages. Inducible nitric oxide synthase (iNOS) and iNOS mRNA were detected by northern blot and western blot, respectively. The cAMP elevating agents Bu2cAMP and prostaglandin E2 each alone did not show any effect on NO production but along with IFN-gamma and lipolysaccharide (LPS) they slightly enhanced NO production. Dexamethasone inhibited NO production in IFN-gamma- and LPS-treated cells; cAMP elevating agents interfered with the NO production inhibited by dexamethasone. Inhibition was revealed at the mRNA level as well as at protein level. Bu2cAMP or dexamethasone either alone or synergistically inhibited IL-12 production; Bu2cAMP interfered with dexamethasone-mediated inhibition of IL-10 production in IFN-gamma- and LPS-treated macrophages. The use of glucocorticoids along with cAMP elevating agents was beneficial in lowering the level of inflammatory mediator IL-12 and producing high levels of the anti-inflammatory mediator IL-10 active in cell protection. On the other hand, interference of Bu2cAMP with dexamethasone-mediated NO inhibition may have adverse effect. Therefore, adverse effects due to cAMP-mediated interference (inhibition) with NO synthesis may occur in many inflammatory diseases during combined drug therapy by glucocorticoids and cAMP elevating agents.
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