XXXX but not -delta agonists inhibit @entity32 in a @entity19 model of asthma: in vitro evidence for an NF-kappaB-independent effect.

@entity1 @entity32 @entity12097 @entity3229 @entity72576 @entity18869 @entity19127 @entity19 @entity5 @entity72577 @entity72578 @entity29852 @entity637
1. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that have been proposed to regulate @entity32 by antagonising the nuclear factor-kappaB (NF-kappaB) signalling pathway. We investigated the role of PPARs using synthetic agonists in @entity19 models of @entity32 , and addressed the possible effect on NF-kappaB signalling in vitro using a @entity1 epithelial cell line, A549. 2. Sensitised BALB/c @entity19 exposed to an aerosol solution of ovalbumin had an increased number of airway eosinophils, neutrophils and lymphocytes. When given intranasally an hour before the aerosol challenge, a @entity3229 ( @entity18869 ) and @entity12097 ( @entity72576 ) selective agonist as well as a dual @entity3229 /gamma ( @entity72577 ) agonist selectively inhibited allergen-induced bronchoalveolar lavage eosinophil and lymphocyte but not neutrophil influx. In contrast, a @entity19127 agonist ( @entity29852 ) was inactive. 3. When given intranasally an hour before challenge, @entity3229 and @entity12097 selective agonists as well as a dual @entity3229 /gamma agonist did not inhibit lipopolysaccharide-induced bronchoalveolar lavage neutrophil influx or @entity5 necrosis factor-alpha ( @entity637 ) and KC production. 4. In A549 cells, selective agonists for @entity3229 -alpha, -gamma and -delta did not inhibit intracellular adhesion molecule-1 expression following stimulation with proinflammatory cytokines. In addition, IL-8 release and the activation of an NF-kappaB-responsive reporter gene construct were inhibited only at micromolar concentrations, suggesting that these effects were not @entity3229 -mediated. 5. Our in vivo data show that agonists of @entity72578 , but not -delta, inhibit allergen-induced bronchoalveolar lavage eosinophil and lymphocyte influx. In vitro data suggest that this effect might not be mediated by antagonism of the NF-kappaB pathway.
