DAMP molecules S100A9 and S100A8 activated by IL‐17A and house‐dust mites are increased in atopic dermatitis

Abstract

Further research is needed to determine the functional role of lymphatic vascular electrotaxis in vivo and to investigate possible applications, including stem cell maintenance (9). ConclusionsDirect-current electrical stimulation promoted both cytoskeleton extension of LECs via the FAK pathway and calcium influx, leading to induction of proliferation and migration of LECs to the cathode in vitro. Electric stimuli could be used to control lymphatic function and its related diseases. AcknowledgementsWe would like to thank Suin Kyo for her technical assistance. K.K and Y.M designed, performed the research study and analysed the data. M.S, K.F, N.S and Y.M performed the research and analysed the data. K.K wrote the paper, Y.T and T.A contributed the development of DC application instrument for the study. Conflict of interestsThe authors have declared no conflicting interests. Supporting InformationAdditional supporting data may be found in the supplementary information of this article. Data S1. Complete materials and methods. Figure S1. Schematic illustration of DC application for migration assay of LECs. Abstract: S100A9 and S100A8 are called damage-associated molecular pattern (DAMP) molecules because of their proinflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house-dust mites affect S100A9 and S100A8 expression in Th2 cytokine-and Th17 cytokine-treated keratinocytes, and how secretion of these molecules affects keratinocyte-derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL-17A-and Dermatophagoides (D.) farinae-treated keratinocytes, respectively. Furthermore, co-treatment with D. farinae and IL-17A strongly increased expression of S100A9 and S100A8 compared with D. farinae-Th2 cytokine co-treatment. The IL-33 mRNA level increased in a dose-dependent manner in S100A9-treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMPmediated inflammation in AD triggered by IL-17A and house-dust mites.

Barrier Epithelial Cells and the Control of Type 2 Immunity

“…These proteins function as intracellular differentiation markers, and upon secretion, they act as amplifiers of inflammatory responses in several inflammatory diseases via two receptors, Toll-like receptor 4 (TLR4) and receptor of advanced glycation endproducts (RAGE), that also binds to HMGB1. S100A9-treated keratinocytes show a dramatic RAGE-dependent increase in the amounts of IL-33 mRNA, whereas no significant changes in TSLP or TNF-a mRNA expression are observed (Jin et al, 2014). The role of these S100 proteins in vivo in relevant type-2-mediated diseases still needs to be fully addressed.…”

“…More recently, the expression of other members of the S100 protein family, S100A8 and S100A9, has also been found to be increased in lesional AD skin (Gittler et al, 2012) and by keratinocytes after exposure to HDM (Jin et al, 2014). These proteins function as intracellular differentiation markers, and upon secretion, they act as amplifiers of inflammatory responses in several inflammatory diseases via two receptors, Toll-like receptor 4 (TLR4) and receptor of advanced glycation endproducts (RAGE), that also binds to HMGB1.…”

The Effects of Antigen-Specific IgG1 Antibody for the Pulmonary-Hypertension-Phenotype and B Cells for Inflammation in Mice Exposed to Antigen and Fine Particles from Air Pollution

“…These markers included: numbers of neutrophils in the BAL, lung expression of the danger associated molecular pattern molecules S100 calcium binding protein A ( S100a)8 , S100a9 [49, 50] and lung expression of IL-6 . IL-6 is significantly increased in the serum of pulmonary hypertension patients [51].…”

Elevated fecal calprotectin levels are associated with severity of atopic dermatitis in children

“…9,10 Increased calprotectin levels have been found in chronic inflammatory bowel disease or allergic diseases. [10][11][12] Fecal calprotectin is a potentially important clinical test as a marker of gastrointestinal tract inflammation and has been increasingly used as a non-invasive marker for the diagnosis of bowel inflammation or gastrointestinal allergic diseases. 10,11,13 Although many studies have reported the relationship between fecal calprotectin and gastrointestinal inflammation or allergic diseases, calprotectin has rarely been studied in AD.…”

“…However, only a few studies have addressed elevated calprotectin levels in the skin or serum in AD. 12,21 Orivuori et al 22 demonstrated that infants with high fecal calprotectin levels at the age of 2 months had an increased risk of developing AD by age 6. They concluded that imbalance of the gut microbiota and intestinal inflammation in early life was associated with later development of AD.…”