ABSTRACT
Recent evidence of gut microbiota dysbiosis in the context of psoriasis and the increased cooccurrence of inflammatory bowel disease and psoriasis suggest a close relationship between skin and gut immune responses. Using a mouse model of psoriasis induced by the Toll-like receptor (TLR) 7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by inflammatory changes in the small intestine associated with eosinophil degranulation, which impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were increased in mice prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells were treated with media containing eosinophil granule proteins and exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by the transfer of eosinophils. Imiquimod levels and the distribution of eosinophils were positively correlated in the intestine. TLR7-deficient mice did not exhibit intestinal eosinophil degranulation but did exhibit attenuated inflammation in the skin and small intestine following imiquimod administration. These results suggest that TLR7-dependent bidirectional skin-to-gut communication occurs in psoriatic inflammation and that inflammatory changes in the intestine can accelerate psoriasis.
Subject(s)
Cell Degranulation , Disease Models, Animal , Eosinophils , Imiquimod , Intestine, Small , Psoriasis , Toll-Like Receptor 7 , Animals , Toll-Like Receptor 7/metabolism , Toll-Like Receptor 7/genetics , Psoriasis/pathology , Psoriasis/metabolism , Mice , Eosinophils/metabolism , Eosinophils/immunology , Humans , Intestine, Small/pathology , Intestine, Small/metabolism , Skin/pathology , Skin/metabolism , Inflammation/pathology , Inflammation/metabolism , Mice, Knockout , Caco-2 Cells , Membrane GlycoproteinsABSTRACT
Despite the high prevalence of chronic dermatitis and the accompanied intractable itch, therapeutics that specifically target itching have low efficacy. Increasing evidence suggests that TLRs contribute to immune activation and neural sensitization; however, their roles in chronic itch remain elusive. Here, we show that the RBL-2H3 mast cell line expresses TLR4 and that treatment with a TLR4 antagonist opposes the LPS dependent increase in mRNA levels of Th2 and innate cytokines. The pathological role of TLR4 activation in itching was studied in neonate rats that developed chronic itch due to neuronal damage after receiving subcutaneous capsaicin injections. Treatment with a TLR4 antagonist protected these rats with chronic itch against scratching behavior and chronic dermatitis. TLR4 antagonist treatment also restored the density of cutaneous nerve fibers and inhibited the histopathological changes that are associated with mast cell activation after capsaicin injection. Additionally, the expression of IL-1ß, IL-4, IL-5, IL-10, and IL-13 mRNA in the lesional skin decreased after TLR4 antagonist treatment. Based on these data, we propose that inhibiting TLR4 alleviated itch in a rat model of chronic relapsing itch, and the reduction in the itch was associated with TLR4 signaling in mast cells and nerve fibers.
ABSTRACT
BACKGROUND AND AIMS: Here, we present the full-length mitogenome sequences of Hemibarbus labeo, Hemibarbus longirostris, and Hemibarbus mylodon - three fish species belonging to the subfamily Gobioninae (Teleostei, Cypriniformes, and Cyprinidae). H. mylodon is endemic to the Korean Peninsula and a critically endangered freshwater species because of various anthropogenic activities around its natural habitat. RESULTS: Overall characteristics of mitogenomes of the three Hemibarbus species were identical to previously known typical vertebrate mitogenomes. Bayesian inference of phylogeny recovered the monophyly of the subfamily Gobioninae with high posterior probability support, with the three Hemibarbus species forming a strongly supported monophyletic group. H. mylodon was placed at the basal position, and H. longirostris was separated from two monophyletic H. labeo types. CONCLUSION: Our findings are congruent with the previous taxonomic appraisal based on morphological analysis.