In vitro effects of XXXX on inducible @entity842 synthase and cyclooxygenase-2 in porcine alveolar macrophages.

@entity1707 @entity39 @entity5 @entity1421 @entity6649 @entity5390 @entity842
OBJECTIVE: To determine the amount of inducible @entity842 synthase (iNOS) and cyclooxygenase-2 (COX-2) activity in alveolar macrophages in response to @entity6649 (APP) by determining @entity842 (NO) and @entity1421 ( @entity1421 ) concentrations. SAMPLE POPULATION: Freshly isolated porcine alveolar macrophages. PROCEDURE: Alveolar macrophages were incubated for 48 hours with APP (1 X 10(4) colony-forming units/mL), interleukin-1beta, (IL-1beta; 5 U/mL), @entity5 @entity39 factor-alpha (TNFalpha; 500 U/mL), interferon-gamma (IFN-gamma, 100 U/mL), or lipopolysaccharide (LPS; 10 microg/mL). In a second experiment, alveolar macrophages were incubated with fresh medium (negative control), APP alone, or APP with 1 of the following: IL-1beta, TNF-alpha, or IFN-gamma. In a third experiment, alveolar macrophages were incubated with fresh medium (negative control), LPS (positive control), APP alone, or APP with 1 of the following: an iNOS inhibitor (3.3 microM), a COX-2 inhibitor (10 microM); or both the iNOS and COX-2 inhibitors. Supernatant was obtained at 0, 3, 6, 9, 12, 24, and 48 hours after treatment for determination of NO and @entity1421 production. RESULTS: The addition of APP to alveolar macrophages resulted in significant increases in NO and @entity1421 production. The addition of APP and IFN-gamma synergistically induced NO production. Inhibition of iNOS and COX-2 decreased NO and @entity1421 production, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro activation of alveolar macrophages by APP results in increased production of NO and @entity1421 . @entity842 and @entity1421 production appears to be largely dependent on iNOS and COX-2 activity. Pharmacologic modulation of iNOS and COX-2 activity may represent a therapeutic target for @entity1707 with @entity5390 .
