In our mouse model of allergen induced airway inflammation, local application selleck of the imiquimod derivative resiquimod via the airways after allergen sensitization but prior to airway allergen challenges inhibited development of eosinophilic airway inflammation and airway hyperreac tivity that was associated with a shift from a predominant Th2 immune response toward a predominant Th1 immune response. 17 Induction of T bet and suppression of GATA 3 were recently described Inhibitors,Modulators,Libraries to be the fundamental and protective mechanisms of imidazoquinolines. 18 Inhibition of Th2 inducing transcription factors can also be performed by so called gene silencing, the inhibition of distinct gene transcription. Oligonucleotide decoys competitively inhibit binding of transcription factors at the deoxyribonucleic acid of specific promoter genes and therefore inhibit transcription of respective genes.

Indeed, inhibition of STAT6 by means of ODN decoys did diminish proliferation of murine and human Th2 cells in vitro19 and did suppress IgE synthesis and development of the late phase inflammatory response in vivo in a mouse model of atopic dermatitis. 20 Although STAT1 directs Th1 immune responses, it also supports development of allergen induced airway inflam mation by enhancing Inhibitors,Modulators,Libraries expression of the costimulatory molecule CD40 on APCs and B cells. CD40 interacts with CD40L on T cells and activates them to produce Th2 cytokines.

In accordance, intranasal application of STAT1 inhibiting Inhibitors,Modulators,Libraries ODN decoys did diminish Th2 cytokine production and expression of IL 4 dependent vascular cell adhesion molecule 1 on endothelial cells, which is known to promote leukocyte infiltration of the airways and therefore did prevent development of allergen induced airway disease in sensitized mice. 21 Further experimental studies are required to analyze the effects of STAT1 on allergen sensitization. Competitive inhibition of production of transcription factors and cytokines at the ribonucleic acid level might also result in diminished Th2 cytokine production. Inhibitors,Modulators,Libraries Specific antisense ODNs containing 15 to 20 ODNs activate ribonuclease H, which splits the RNA rest out of DNA RNA double strands and therefore degrades target messenger RNA, or antisense ODNs inhibit translation via steric blockade of ribosomes.

Inhibitors,Modulators,Libraries In fact, in a mouse model, local application figure 1 of specific antisense ODNs did diminish expression of GATA 3, which resulted in dramatically suppressed Th2 cytokine production and allergen mediated airway inflammation. 23 In contrast, suppression of STAT6 by antisense ODN decoys showed divergent therapeutic effects in vitro and in vivo. 24,25 Compared to antisense ODN decoys, the small interfer ing ribonucleic acid technique promises to be more efficient. Specific endonucleases, so called dicer enzymes, split long double strand RNA into siRNA containing 21 to 23 nucleotides.