Platelet-activating factor blockade inhibits the T-helper type 17 cell pathway and suppresses psoriasis-like skin disease in K5.hTGF-β1 transgenic mice.

摘要: Platelet-activating factor (PAF), a potent biolipid mediator, is involved in variety of cellular transduction pathways and plays prominent role inducing inflammation different organs. We used K5.hTGF-β1 transgenic mice, which exhibit an inflammatory skin disorder molecular cytokine abnormalities with strong similarities to human psoriasis, study the pathogenic PAF. found that injecting PAF into mice led accelerated manifestation psoriatic phenotype by local effect. In contrast, receptor antagonist PCA-4248 lowered level (most likely depressing autocrine loop) neutrophil, CD68+ cell (monocyte/macrophage), CD3+ T-cell accumulation blocked progression psoriasis-like phenotype. This effect blockade was specific similar psoralen–UV-A paralleled decrease abnormally elevated mRNA and/or protein levels T-helper type 17 cell–related cytokines IL-17A, IL-17F, IL-23, IL-12A, IL-6 its transcription signal transducer activator 3. treatment up-regulated cyclooxygenase-2 IL-10 dorsal release serum skin. Interfering may offer opportunity develop novel therapeutic strategies for psoriasis associated comorbidities, including metabolic syndrome atherosclerosis, IL-17 axis be involved.