Immunopathogenesis and management of polymorphic light eruption.

Polymorphic light eruption (PLE) is the most common immunologically mediated photodermatosis, demonstrating many abnormalities caused by critical failure of ultraviolet (UV)-induced immunosuppression. The unique expression of antimicrobial peptides in PLE, which is most likely determined by alteration of microbiome components upon UV exposure, implicates their possible triggering role and pathogenic significance in the eruption. The review aims to clarify current knowledge regarding the immunological disturbances correlated with PLE that serve a base for better understanding of molecular pathogenesis of the disease and the development of new therapeutic strategies. Preventive treatment with broad-spectrum suncreens and sunscreens containing DNA repair enzymes, as well as natural photohardening with graduate exposure to sunlight in early spring could be sufficient in milder cases. Antioxidants and topical calcipotriol are promising approach for adjuvant prevention. Phototherapy, mainly with narrow band UVB rays, is more appropriate method in severe cases of the disease. The established treatment options for PLE include local and systemic glucocorticoids, systemic nonsedative antihistamines for itch relief, and rarely, immunosuppressive drugs in the refractory cases. Like medical photohardening, afamelanotide has the potential of photoprotection by inducing a melanization of the skin. Afamelanotide is believed to be a possible new treatment option for very severe and refractory cases of PLE. Targeting the main pruritogenic cytokine, IL-31, opens a new road for the development of novel therapeutic approaches to combat moderate and severe itching in cases of PLE with intense pruritus.

IL-31 transgenic mice show reduced allergen-induced lung inflammation.

Interleukin-31 (IL-31) is a Th2 cell-derived cytokine that has been closely linked to pruritic skin inflammation. More recently, enhanced IL-31 serum levels have also been observed in patients with allergic rhinitis and allergic asthma. Therefore, the main aim of this study was to unravel the contribution of IL-31 to allergen-induced lung inflammation. We analyzed lung inflammation in response to the timothy grass (Phleum pratense) pollen allergen Phl p 5 in C57BL/6 wild-type (wt) mice, IL-31 transgenic (IL-31tg) mice, and IL-31 receptor alpha-deficient animals (IL-31RA-/- ). IL-31 and IL-31RA levels were monitored by qRT-PCR. Cellular infiltrate in bronchoalveolar lavage fluid (BALF) and lung tissue inflammation, mucus production as well as epithelial thickness were measured by flow cytometry and histomorphology. While allergen challenge induced IL-31RA expression in lung tissue of wt and IL-31tg mice, high IL-31 expression was exclusively observed in lung tissue of IL-31tg mice. Upon Phl p 5 challenge, IL-31tg mice showed reduced numbers of leukocytes and eosinophils in BALF and lung tissue as well as diminished mucin expression and less pronounced epithelial thickening compared to IL-31RA-/- or wt animals. These findings suggest that the IL-31/IL-31RA axis may regulate local, allergen-induced inflammation in the lungs.

Luteolin suppresses IL-31 production in IL-33-stimulated mast cells through MAPK and NF-κB signaling pathways.

IL-31 and IL-33 are cytokines, which are expressed in many inflammatory and pathological disorders, thus suggesting an IL-31/IL-33 axis interaction in pathological diseases. Luteolin from natural products is known for its anti-inflammatory activities associated with the regulation of inflammatory signaling pathways. Here, we investigated the effects of luteolin in the regulation of IL-33-stimulated production and secretion of IL-31 in HMC-1.2 mast cells. Human mast cells (HMC-1.2) were treated with luteolin and stimulated with IL-33. Real-time PCR was used to measure IL-31 mRNA expression. Western blot and immunofluorescence assays were used to measure IL-31 expression. ELISA techniques were used to measure IL-31 secretion and NF-κB-DNA-binding activities. The results revealed that luteolin inhibited the expression of IL-31 in IL-33-stimulated HMC-1.2 cells at the mRNA and protein levels. Also, Luteolin inhibited the secretion of IL-31 into the cell culture media of the IL-33-stimulated HMC-1.2 cells. Further findings demonstrated that luteolin inhibited the activation of ERK, JNK, p38, and NF-κB p65 in the IL-33-stimulated HMC-1.2 cells. In addition, luteolin also prevented the nuclear translocation and binding of p65 to its DNA-binding site. Based on the results, luteolin may be considered as a potential therapeutic or functional food agent for the prevention and/or treatment of IL-31 and IL-33-related diseases.

Soybean Fermented with Bacillus amyloliquefaciens (Cheonggukjang) Ameliorates Atopic Dermatitis-Like Skin Lesion in Mice by Suppressing Infiltration of Mast Cells and Production of IL-31 Cytokine.

The present study was conducted with the aim to investigate the ameliorative effects of a new soybean product (cheonggukjang) fermented with Bacillus amyloliquefaciens SCGB1 (SFBA) in atopic dermatitis (AD) mouse model. Visual evaluation of AD induction in the mice indicated the remarkable control of SFBA in reducing the pathological severity of AD-like skin lesions reported as the SCORAD score of AD clinical symptoms. The results revealed that SFBA reduced dorsal skin and epidermal thickness to a similar extent with prednisolone. Further analysis revealed the dominance of SFBA in restraining mast cell infiltration in the dermis; immunoglobulin-E expression in serum; and TH2 IL-4 cytokine and itch-related IL-31 cytokine in the mice skin and serum. SFBA also suppressed scratching behaviours in mice induced by compound 48/80. Further histological findings also revealed the alleviation of collagen fiber deposition in dermal skin of the AD mice model. These actions of SFBA were examined to be mediated by its suppression of the phosphorylation activation of key signalling molecules such as NF-kappaB and MAPK responsible for the induction of cytokine production. Thus, SFBA can be considered as a promising functional food for managing clinical, histological and immunological spectra associated with AD.

Gamisasangja-tang suppresses pruritus and atopic skin inflammation in the NC/Nga murine model of atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Gamisasangja-tang (GST) is a traditional herbal formula prescribed for patients with intractable pruritus in association with various inflammatory skin diseases. To evaluate the effects of GST on pruritic skin inflammation and investigate its cellular and molecular mechanisms. MATERIALS AND METHODS: We orally administered GST to NC/Nga (NC) mice, an animal model of atopic dermatitis. Scratching frequency and the dermatitis index were evaluated, and histological examination was performed using hematoxylin and eosin and toluidine blue staining. The levels of interleukin (IL)-31 and T-helper cell type 2 (TH2) cytokines were determined in both the dorsal skin and cultured splenocytes by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The serum levels of chemokines and immunoglobulin E (IgE) were determined by ELISA. Changes in the inflammatory cell population were analyzed by a hemocytometer. RESULTS: GST significantly lowered scratching frequency and inhibited increases in dermatitis index, thickness of epidermis/dermis and infiltration of chemokine (C-C motif) receptor 3 (CCR3)(+) and cluster of differentiation (CD)117(+)/FcεRIα (Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide)(+) cells in atopic skin. Both IL-31 mRNA expression and production were significantly reduced by GST, which was accomrease in the levels of IL-4, IL-5, and IL-13. Further, GST treatment suppressed the secretion of eotaxin, TARC (thymus and activation-regulated chemokine), IgE, and increases in the number of basophils and eosinophils in the blood. CONCLUSION: GST may have potential as an effective treatment for pruritic skin disease such as atopic dermatitis.