Psoriasis: A review of the role of serotonergic system

Psoriasis, a chronic inflammatory skin disease, is not yet curable, and its precise causes remain unclear. Nevertheless, several lines of evidence support that psoriasis is a multifactorial disease. Because psoriasis occurs in connection with stress and mood disorders, the genes in serotonergic system may be involved in psoriasis with regard to etiology and pathogenesis. Such molecular impacts supported by scientific evidence on serotonergic gene expression changes and genetic polymorphisms have been increasingly highlighted. The serotonergic system has also received considerable attention as a potential target for the therapy of psoriasis. Here, we summarize the current knowledge about role of genes in serotonergic system in psoriasis and point out possible directions of future studies

New polymorphisms associated with response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis

Anti-tumor necrosis factor (anti-TNF) drugs are effective against psoriasis, although 20–30% of patients are nonresponders. Few pharmacogenomic studies have been performed to predict the response to anti-TNF drugs in psoriasis. We studied 173 polymorphisms to establish an association with the response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis (N=144). We evaluated the response using PASI75 at 3, 6 and 12 months. The results of the multivariate analysis showed an association between polymorphisms in PGLYR4, ZNF816A, CTNNA2, IL12B, MAP3K1 and HLA-C genes and the response at 3 months. Besides, the results for polymorphisms in IL12B and MAP3K1 were replicated at 6 months. We also obtained significant results for IL12B polymorphism at 1 year. Moreover, polymorphisms in FCGR2A, HTR2A and CDKAL1 were significant at 6 months. This is the first study to show an association with these polymorphisms. However, these biomarkers should be validated in large-scale studies before implementation in clinical practiceThis study was supported by Instituto de Salud Carlos III (FIS PI10/01740), Fundación Teófilo Hernando, and AbbVie. RPP has a grant from Universidad Autónoma de Madrid (FPI program 2013

Decreased EGFR mRNA expression in response to antipsoriatic drug dithranol in vitro

Dithranol is enormously effective in the treatment of psoriasis; however its molecular mode of action should be further elucidated. Since epidermal growth factor receptor (EGFR) is involved in the pathogenesis of psoriasis, the objective of this study was to investigate the transcriptional effect of dithranol on EGFR gene expression in the HaCaT keratinocyte cell line, which is commonly employed as a model system to study psoriasis including experiments examining the effects of therapeutic drugs and cellular regulators on keratinocytes. Cultured HaCaT cells were treated with 0.1-0.5 ìg/ml dithranol for 30 min. After 4 h, total cellular RNA isolated from HaCaT cells was reverse transcribed to cDNA which was subjected to polymerase chain reaction (PCR) with specific primer pair for EGFR. We found that dithranol treatment down-regulated the EGFR mRNA of HaCaT cells in a concentration-dependent manner. Our result was further substantiated using a quantitative real-time PCR approach. Taken together, the dithranol-induced down-regulation of the EGFR in cultured human keratinocytes might help to disclose the molecular therapeutic action of the drug