Serum sphingosine‐1‐phosphate is elevated in atopic dermatitis and associated with severity

Abstract

4. Kim RY, Horvat JC, Pinkerton JW, et al. MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2.

Altered Serum Phospholipids in Atopic Dermatitis and Association with Clinical Status

“…This study consisted of three groups: healthy controls (n = 47), those with AD (n = 179), and those with non-AD with atopic comorbidities (i.e., non-AD with allergic rhinitis, bronchial asthma, and/or food allergy, n = 22). We recruited these participants as a part of the Christine Kühne-Center for Allergy Research and Education (Davos, Switzerland) program ( Bieber et al., 2020 ), who were the same as those recruited in our previous study ( Sakai et al., 2021 ). We evaluated the serum concentrations of 40 lipids in all participants ( Table 1 ).…”

“…Several serum levels of phospholipids were altered in the AD group compared with those in the other groups; lipids exhibiting the apparent changes included increased Sph and multiple variants of PC and decreased Cer(16:0) in patients with AD. Moreover, serum levels of Sph, correlating with body surface area and thymus and activation-regulated chemokine, were elevated in moderate to severe AD, such as circulating S1P in AD ( Sakai et al., 2021 ). Sph and Cer(16:0) were also detected as the risk-increasing effect and risk-reduction effect of AD, respectively.…”

“…Furthermore, disturbances in circulating sphingolipids levels and their association with the phenotype have been observed in inflammatory and allergic disorders, such as systemic lupus erythematosus ( Watson et al., 2012 ), psoriasis ( Kowalski et al., 2013 ; Myśliwiec et al., 2017 ), or bronchial asthma ( Kim et al., 2020 ; Kowal et al., 2019 ). Recently, we reported that serum concentrations of sphingosine (Sph)-1-phosphate (S1P), which is a bioactive lipid mediator, in patients with AD are higher than those in healthy individuals and patients without AD with atopic comorbidities ( Sakai et al., 2021 ). S1P receptors are therapeutic targets in multiple disorders ( Cartier and Hla, 2019 ), and the clinical trials with the compounds targeting S1P receptors in patients with AD are underway (NCT04162769, ACTRN12617000763347).…”

Atopic dermatitis: an expanding therapeutic pipeline for a complex disease

“…This goal can be reached by modulation of their receptors for sphingosine 1-phosphate (S1P), the active terminal derivative of sphingosine metabolism. S1P acts via gradients in circulatory fluids and has been reported to be increased in various conditions such as multiple sclerosis and neurodegeneration 158 , pneumonia 159 , psoriasis 160 , asthma 161 and more recently in AD 162 . The multiple biological activities of S1P are mediated by five distinct G protein-coupled receptors (S1PR1-5), which are differently expressed in various tissues 163 .…”

Novel functions of S1P in chronic itchy and inflammatory skin diseases

“…S1P serum levels have recently been found to be highly increased in AD patients, especially those with an eczema area and severity index (EASI) ≥ 16. S1P serum levels also correlate with the EASI score 61 . Furthermore, S1P lyase mRNA levels have been observed to be increased in lesional canine AD skin, when compared to healthy skin, indicating an increased degradation of S1P and therefore diminished S1P levels 62 .…”