Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters

Database
Language
Affiliation country
Publication year range
1.
Am J Pathol ; 178(2): 699-708, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21281802

ABSTRACT

Platelet-activating factor (PAF), a potent biolipid mediator, is involved in a variety of cellular transduction pathways and plays a prominent role in inducing inflammation in different organs. We used K5.hTGF-ß1 transgenic mice, which exhibit an inflammatory skin disorder and molecular and cytokine abnormalities with strong similarities to human psoriasis, to study the pathogenic role of PAF. We found that injecting PAF into the skin of transgenic mice led to inflammation and accelerated manifestation of the psoriatic phenotype by a local effect. In contrast, injecting mice with PAF receptor antagonist PCA-4248 lowered the PAF level (most likely by depressing an autocrine loop) and neutrophil, CD68(+) cell (monocyte/macrophage), and CD3(+) T-cell accumulation in the skin and blocked progression of the psoriasis-like phenotype. This effect of PAF blockade was specific and similar to that of psoralen-UV-A and was paralleled by a decrease in abnormally elevated mRNA and/or protein levels of T-helper type 17 cell-related cytokines IL-17A, IL-17F, IL-23, IL-12A, and IL-6 and its transcription factor signal transducer and activator of transcription 3. In contrast, PCA-4248 treatment up-regulated mRNA levels of cyclooxygenase-2 and IL-10 in dorsal skin and release of IL-10 in serum and skin. Interfering with PAF may offer the opportunity to develop novel therapeutic strategies for inflammatory psoriasis and associated comorbidities, including metabolic syndrome and atherosclerosis, in which the IL-17 axis may be involved.


Subject(s)
Platelet Activating Factor/antagonists & inhibitors , Psoriasis/pathology , Signal Transduction , Th17 Cells/metabolism , Transforming Growth Factor beta1/genetics , Animals , Cytokines/genetics , Cytokines/metabolism , Dihydropyridines/administration & dosage , Dihydropyridines/pharmacology , Disease Progression , Down-Regulation/drug effects , Humans , Mice , Mice, Transgenic , PUVA Therapy , Phenotype , Platelet Activating Factor/metabolism , Platelet Membrane Glycoproteins/antagonists & inhibitors , Platelet Membrane Glycoproteins/metabolism , Psoriasis/drug therapy , Psoriasis/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Skin/drug effects , Skin/metabolism , Skin/pathology , Th17 Cells/drug effects , Th17 Cells/immunology , Transforming Growth Factor beta1/metabolism , Up-Regulation/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL