Persistent and relapsing itch commonly manifests in inflammatory skin disorders such as atopic dermatitis (AD). AD pathogenesis is driven by interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13). Dupilumab, a monoclonal antibody blocking the action of IL‐4 and IL‐13 effectively reduces the symptoms of AD and itch. Little is known whether IL‐4 and IL‐13 directly contribute to itch transduction. A recently published study (Oetjen et al, Cell, 2017, 171, 217) found IL‐4 and IL‐13 to directly activate itch‐sensory neurons in vitro. Surprisingly, they found no significant increase in scratching after intradermally injecting high doses (2.5 ug/ml) of IL‐4 and IL‐13 into mice. Similar experiments in our lab, however, suggested that both IL‐4 and IL‐13 contribute to acute itch in vivo. We intradermally injected lower doses (1 ug/ml) of IL‐4 and IL‐13 into mice and found a significant increase of scratching bouts compared to vehicle. Interestingly, the combined treatment of IL‐4 and IL‐13 produced additive increase of scratching and acute pruritus at an earlier time point compared to each cytokine administered alone. In summary, our study shows a rapid and significant increase of scratching after intradermal injection of IL‐4, IL‐13 or combined IL‐4/ IL‐13 compared to vehicle in mice 5‐10 minutes after injection. Our data suggest that IL‐4 and IL‐13 alone and combined directly act as potent acute pruritogens on sensory nerves. This finding expands our understanding of cytokines as pruritogens, how targeted anticytokine medications act in AD, and about neuroimmune communication in the skin.
Background West Virginia (WV) has one of the highest national rates of obesity, especially among middleaged men, and one of the lowest Registered Dietitian Nutritionist (RDN) ratios per capita. Providing nutrition advice via teleconferencing may allow obese WV middle-aged men to overcome access barriers that are preventing them from overcoming obesity. However, before large-scale interventions can be effectively conducted, the feasibility must be assessed. Objective The purpose of this study is to evaluate the feasibility of a home telenutrition weight-loss program using videoconferencing among obese men in WV. Feasibility is assessed through technical difficulties tracked throughout the intervention and through a post-intervention satisfaction survey. Methods A survey was developed to assess the participants' level of satisfaction related to the technological and nutritional care aspects of the intervention. Twenty-seven men aged 40-70 who participated in a 12-week telenutrition weight loss intervention took this survey upon completion of the intervention. The amount and type of technical difficulties were also documented throughout the intervention. Results Eighty-one video calls were attempted throughout the intervention with all but one participant experiencing at least one minor or major technical difficulty either logging on or during the calls. Even with these technical difficulties, overall satisfaction with this mode of delivery was high, regardless of age, income level, education level, employment status, and technical difficulties logging on or during video calls. Previous videoconferencing experience was significantly related to higher satisfaction levels. Conclusion and summary Videoconferencing is a technologically feasible and highly acceptable method of nutrition counseling for the middle-aged, obese male population in WV, as shown with no significant differences between group demographics. Videoconferencing should be used to develop a largerscale intervention for this population to combat obesity within this demographic.
Little is known about the roles of microRNAs in the pathogenesis of psoriasis. The aim of this study was to investigate the function of miR-146a in keratinocytes in relation to psoriasis. The expression of miR-146a and target genes in the skin of psoriasis patients and in stimulated and unstimulated primary keratinocytes from human and miR-146a-/-mouse was investigated. The expression of miR-146a was confirmed to be increased in lesional skin of psoriasis patients with RT-qPCR and in situ hybridization. The expression of miR-146a target genes that are known to regulate inflammatory responses, such as IRAK1, CARD10 and CCL5 were found to be altered in the skin of psoriasis patients. miR-146a was induced in response to psoriasis-associated cytokines IL-17A, TNF-a and IL-1b both in human and mouse primary keratinocytes. When stimulated with IL-17A and TNF-a, several pro-inflammatory factors, such as CCL5, CARD10, CXCL1 and CXCL2 were increased in miR-146a-/-keratinocytes when compared to keratinocytes from wild type mouse. Our data suggest that pro-inflammatory cytokines upregulate the expression of miR-146a in the skin lesions of psoriasis patients where miR-146a helps to reduce inflammatory responses.
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