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
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12630324
DOI
10.1007/bf02818676
Knihovny.cz E-resources
- MeSH
- Macrophage Activation drug effects physiology MeSH
- Cyclic AMP metabolism MeSH
- Anti-Inflammatory Agents pharmacology MeSH
- Dexamethasone pharmacology MeSH
- Bucladesine pharmacology MeSH
- Nucleic Acid Hybridization MeSH
- Interferon-gamma pharmacology MeSH
- Interleukin-10 biosynthesis MeSH
- Interleukin-12 biosynthesis MeSH
- Lipopolysaccharides pharmacology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Blotting, Northern MeSH
- Nitric Oxide biosynthesis MeSH
- Macrophages, Peritoneal drug effects enzymology metabolism MeSH
- RNA chemistry genetics MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase genetics metabolism MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cyclic AMP MeSH
- Anti-Inflammatory Agents MeSH
- Dexamethasone MeSH
- Bucladesine MeSH
- Interferon-gamma MeSH
- Interleukin-10 MeSH
- Interleukin-12 MeSH
- Lipopolysaccharides MeSH
- Nos2 protein, mouse MeSH Browser
- Nitric Oxide MeSH
- RNA MeSH
- Nitric Oxide Synthase Type II MeSH
- Nitric Oxide Synthase 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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