Search

S1P is a pleotropic sphingolipid signalling molecule that acts through binding to five high‐affinity G‐protein coupled receptors. S1P‐signaling affects cell fate in a multitude of ways, e.g. influencing cell differentiation, proliferation, and apoptosis, as well as playing an important role in immune cell trafficking. Though many effects of S1P‐signaling in the human body have been discovered, the full range of functions is yet to be understood. For inflammatory skin diseases such as atopic dermatitis and psoriasis, evidence is emerging that dysfunction and imbalance of the S1P‐axis is a contributing factor. Multiple studies investigating the efficacy of S1PR modulators in alleviating the severity and symptoms of skin conditions in various animal models and human clinical trials have shown promising results and validated the interest in the S1P‐axis as a potential therapeutic target. Even though the involvement of S1P‐signalling in inflammatory skin diseases still requires further clarification, the implications of the recent findings may prompt expansion of research to additional skin conditions and more S1P‐axis modulatory pharmaceuticals. [ABSTRACT FROM AUTHOR]

Several studies have shown that neurotrophins including brain-derived neurotrophic factor ( BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis ( AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein ( ECP), total IgE, IL-4, IL-13 and IL-31 in children with AD ( n = 56) compared to nonatopic healthy children ( n = 25). In addition, we analyzed FLG loss-of-function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin-positive or filaggrin-negative children with AD, and there was no correlation of BDNF with IL-31 and Th2 cytokines including IL-4 and IL-13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil-, but not Th2-dependent manner. [ABSTRACT FROM AUTHOR]

Background Recent studies suggest that neurotrophins have a pivotal role in neuroimmune interactions. Indeed, in contrast to nonatopic subjects (NA), neurotrophins have been shown to be increased in atopic diseases such as allergic rhinitis (AR) and atopic dermatitis (AD). Aim The aim of the study was to assess the functional role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3 and -4 and the expression of pan-neurotrophin receptor (p75NTR) and tyrosine kinase (trk)A, -B and -C on peripheral blood eosinophils in AR, AD and NA. Methods Peripheral blood eosinophils of patients with AR, AD and NA were purified by CD16 negative selection (purity>98%). Neurotrophin receptor expression was analysed by FACS analysis. Apoptosis test (FACS analysis) and chemotactic index (modified Boyden chamber assay) were assessed after stimulation with BDNF, NT-3/-4 and NGF. Results The expression of trkA-C and p75NTR was significantly higher in AD>AR>NA ( P<0.05–0.001). Apoptosis was significantly inhibited by BDNF, NGF, NT-3 in AD ( P<0.05–0.001), by NT-3/-4 and NGF in AR ( P<0.05–0.01) and by NT-3 ( P<0.05–0.01) in NA eosinophils. Chemotaxis was significantly induced by BDNF and NT-3/4 ( P<0.01–0.001) in AD peripheral blood eosinophils. Conclusion Neurotrophin receptor expression and neurotrophin functional activity was greatest in AD>AR>NA. AD eosinophils are pre-activated and may therefore better respond to neurotrophins. With this study, we provide new pathophysiologic insights into atopic diseases with a functional role of neurotrophins in peripheral blood eosinophils in AD and AR. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shed light on the complex regulation of genetic, environmental, immunologic and pharmacologic factors, which contribute to the development of atopic dermatitis (AD). However, it is still unclear to which extent neuroimmune mediators have a role in AD. Aims of the study: To assess peripheral neurotrophin levels and their correlation with scoring atopic dermatitis (SCORAD) scores in both the intrinsic and extrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects. Methods: Levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were assessed in peripheral blood with enzyme-linked immunosorbent assay. Based on IgE-mediated sensitization, AD was divided into the extrinsic and intrinsic type. Severity of AD was assessed with SCORAD score and with psoriasis area and severity index (PASI) in patients with psoriasis. Results: Brain-derived neurotrophic factor and NGF were detectable in all the subjects studied. However, the levels of both neurotrophins were significantly higher in patients with extrinsic and intrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects (NGF: P < 0.001, BDNF: P < 0.001). NGF and BDNF levels were similar in the intrinsic and extrinsic type of AD. There was a significant correlation between BDNF and SCORAD score only in patients with the intrinsic type of AD ( r = 0.57, P < 0.05). Conclusions: This study shows for the first time that NGF and BDNF are increased in both, the extrinsic type and the intrinsic type of AD. This finding points to a similar pathophysiologic background implicating a neuroimmune network in both variants of this chronic inflammatory skin disease. Future studies are needed to show the direct mechanisms of neurotrophin action in chronic inflammatory skin. [ABSTRACT FROM AUTHOR]