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 |
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Authors: | Mittal J Dogra N Dass R Majumdar S |
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Institution: | (1) Institute of Microbial Technology, Council of Scientific and Industrial Research, 160 036 Chandigarh, India |
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Abstract: | The effects of cAMP-elevating agents,N
6-2′-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-γ and lipolysaccharide (LPS) they slightly enhanced
NO production. Dexamethasone inhibited NO production in IFN-γ-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-γ-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, inteference 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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