Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Singh, TP; Huettner, B; Koefeler, H; Mayer, G; Bambach, I; Wallbrecht, K; Schön, MP; Wolf, P.
Platelet-activating factor blockade inhibits the T-helper type 17 cell pathway and suppresses psoriasis-like skin disease in K5.hTGF-β1 transgenic mice.
Am J Pathol. 2011; 178(2):699-708
Doi: 10.1016/j.ajpath.2010.10.008
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- Leading authors Med Uni Graz
- Singh Tej Pratap
- Wolf Peter
- Co-authors Med Uni Graz
- Köfeler Harald
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- 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-β1 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cytokines - genetics
- Dihydropyridines - administration & dosage
- Disease Progression -
- Down-Regulation - drug effects
- Humans -
- Mice -
- Mice, Transgenic -
- PUVA Therapy -
- Phenotype -
- Platelet Activating Factor - antagonists & inhibitors
- Platelet Membrane Glycoproteins - antagonists & inhibitors
- Psoriasis - drug therapy
- RNA, Messenger - genetics
- Receptors, G-Protein-Coupled - antagonists & inhibitors
- STAT3 Transcription Factor - metabolism
- Signal Transduction - drug effects
- Skin - drug effects
- Th17 Cells - drug effects
- Transforming Growth Factor beta1 - genetics
- Up-Regulation - drug effects