UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling

At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca²⁺ response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain.The surface epithelium (epidermis) of skin provides barrier protection against dehydration and the potentially harmful external environment (1). Accordingly, skin is the site of first interaction between ambient environment and immunologically competent organismal structures, and also the site for sentient responses (2). Sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are endowed with sensory transduction capacity for heat, cold, mechanical cues, itch, and pain, and their axons directly interface with skin epithelium (2–4).Against a background of suggestive findings (2, 5–7), we wondered whether the epidermis as a “forefront” of sensory signaling may function in sensitizing pain transduction in response to naturally occurring irritating cues. To elucidate mechanisms, we used a mouse sunburn model and induced a state of lowered sensory thresholds associated with tissue injury caused by UV radiation (8–10). UV-sunburn-evoked lowering of sensory thresholds shares major hallmarks of pathological pain, a valuable feature of this model. Skin tissue injury caused by UVB has been elucidated to be mediated by cytokines and chemokines, known from immunological responses, such as IL-1β and IL-6, which are also known to cause and facilitate pain (11–19). Another more recent study identified a proinflammatory chemokine, CXCL5, as proalgesic in response to UVB overexposure of rat and human skin (20). An exciting new arena pertaining to molecular mechanisms of the skin’s response to noxious UV was recently opened by an elegant study that reported the role of UVB-mediated damage to noncoding RNA molecules in the skin (21). Unraveling a molecular mechanism, the Toll-like receptor 3 gene was found critical in signaling the proinflammatory actions of the UVB-damaged noncoding RNA molecules. However, this study focused on molecular mechanisms of acute inflammation in the skin.We intended to identify pain mechanisms that mediate the pain associated with UVB-mediated tissue injury. Pain in response to external environmental cues has been understood better because of scientific progress in the field of transient receptor potential (TRP) ion channels that have been found responsive to such cues, and which were found expressed in DRG and TG peripheral sensory neurons, which are the cells believed to be the primary transducers. Indeed, TRPV1, one of the founding members of the TRPV channel subfamily, has been identified as relevant for pain, including pathological pain, response to thermal cues, and most recently for itch (22–31). However, TRPA1 (transient receptor potential ion channel, ankyrin subfamily, family member #1) and TRPM8 seem to be involved in transduction of pain-inducing stimuli as well (32–36).Also a family member of the TRPV subfamily, TRPV4 is a multimodally activated, nonselective cation channel that is involved in physiological pain evoked by osmotic and mechanical, but not thermal, cues (37–40). For pathological pain, it is relevant for inflammation- and nerve-damage-induced pain sensitization (41–43). Of note, Trpv4^−/− mice exhibit impaired skin-barrier function (44, 45). That said, TRPV4 is expressed in a number of different cell types, including robust expression in epidermal keratinocytes and also is detectable in skin-innervating sensory neurons. This “dual-location expression” of TRPV4 leaves the cellular mechanisms involved in the channel’s function and the functional contribution of environment-exposed keratinocytes vs. skin-innervating sensory neurons unclear.Against this background of dual-location TRPV4 expression and the role of TRPV4 in inflammatory and neuropathic pain, we now address whether epidermally derived TRPV4 is pathophysiologically relevant in sunburn pain and tissue damage. Using Trpv4 gene-targeted mice, selectively inducing targeting in postnatal keratinocytes, and topically applying selective TRPV4 inhibitors, we demonstrate that epidermal TRPV4 plays a prominent, hitherto unrecognized role in UVB-evoked skin tissue damage and pain of sunburn.     

In Contrast to Chlamydia trachomatis,Waddlia chondrophila Grows in Human Cells without Inhibiting Apoptosis,Fragmenting the Golgi Apparatus,or Diverting Post-Golgi Sphingomyelin Transport

The Chlamydiales are an order of obligate intracellular bacteria sharing a developmental cycle inside a cytosolic vacuole, with very diverse natural hosts, from amoebae to mammals. The clinically most important species is Chlamydia trachomatis. Many uncertainties remain as to how Chlamydia organizes its intracellular development and replication. The discovery of new Chlamydiales species from other families permits the comparative analysis of cell-biological events and may indicate events that are common to all or peculiar to some species and more or less tightly linked to “chlamydial” development. We used this approach in the infection of human cells with Waddlia chondrophila, a species from the family Waddliaceae whose natural host is uncertain. Compared to C. trachomatis, W. chondrophila had slightly different growth characteristics, including faster cytotoxicity. The embedding in cytoskeletal structures was not as pronounced as for the C. trachomatis inclusion. C. trachomatis infection generates proteolytic activity by the protease Chlamydia protease-like activity factor (CPAF), which degrades host substrates upon extraction; these substrates were not cleaved in the case of W. chondrophila. Unlike Chlamydia, W. chondrophila did not protect against staurosporine-induced apoptosis. C. trachomatis infection causes Golgi apparatus fragmentation and redirects post-Golgi sphingomyelin transport to the inclusion; both were absent from W. chondrophila-infected cells. When host cells were infected with both species, growth of both species was reduced. This study highlights differences between bacterial species that both depend on obligate intracellular replication inside an inclusion. Some features seem principally dispensable for intracellular development of Chlamydialesin vitro but may be linked to host adaptation of Chlamydia and the higher virulence of C. trachomatis.     

Post-migration dietary changes among African refugees in Geneva: a rapid assessment study to inform nutritional interventions

Objectives: To conduct an assessment of perceived dietary changes and problems by African asylum seekers, in order to develop appropriate nutritional education interventions.Methods: A cross-sectional qualitative study among a convenience sample. Analysis compared and contrasted reported dietary changes and migration-related difficulties.     

Biodegradation of s-triazine compounds by a stable mixed bacterial community.

The potential for biodegradation of s-triazine pesticides was investigated in laboratory batch and sequence batch experiments using a stable mixed bacterial community enriched on atrazine. The experiments were performed aerobically in a mineral salt solution complemented with a mixture of s-triazines as sole carbon and energy sources. Comparisons were made between the efficiency of the inoculum for atrazine degradation in mineral salt solution and in wastewater. In batch cultivation, atrazine, simazine, hydroxyatrazine, and terbutylazine were degraded to concentrations below 0.1 mg/liter after 6 days; evidence of the mineralization was the detection of 14CO2 from [U-ring-14C] atrazine and the production of nitrate and chloride ions. The low degradation rate observed for cyanuric acid and desethylatrazine suggests that degradation proceeded via N-dealkylation and dechlorination. Nevertheless, degradation of ametryne and cyromazine presume the involvement of other degradation pathways. Evidence was given that presence of other additional carbon sources is not an obstacle to atrazine biodegradation, since better results were obtained using wastewater.     

Post-migration dietary changes among african refugees in Geneva: a rapid assessment study to inform nutritional interventions

Summary. Objectives: To conduct an assessment of perceived dietary changes and problems by African asylum seekers, in order to develop appropriate nutritional education interventions.Methods: A cross-sectional qualitative study among a convenience sample. Analysis compared and contrasted reported dietary changes and migration-related difficulties.Results: Nineteen interviews were analysed. After migration, main dietary changes were the decrease in different fruits and vegetables consumed weekly from 10 to 2 and 17 to 10 respectively. The number of respondents drinking sweetened beverages more than 3 times a week increased from 3 to 18. Reasons for changes were related to prices, taste, choice and accessibility.Conclusion: These dietary changes may have serious health consequences. Future remedial interventions based on suggestions of the respondents could easily be implemented.

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Zusammenfassung. Ernährungsveränderungen von afrikanischen Flüchtlingen nach deren Migration nach Genf: eine kurze Ernährungserhebung zur Entwicklung von ErnährungsinterventionenFragestellung: Erhebung von individuell wahrgenommenen Ernährungsveränderungen und -problemen bei afrikanischen Asylsuchenden, um zielgruppenspezifische Ernährungserziehungsmassnahmen entwickeln zu können.Methoden: Eine qualitative Querschnittstudie in einer zweckbestimmten Stichprobe. In den Analysen wurden berichtete Ernährungsveränderungen den migrationsbedingten Schwierigkeiten vergleichend gegenübergestellt.Ergebnisse: Neunzehn Interviews wurden analysiert. Nach der Migration nahm die Anzahl der verschiedenen wöchentlich verzehrten Früchte und Gemüse von 10 auf zwei bzw. von 17 auf 10 ab. Die Zahl der Studienteilnehmer, die häufiger als dreimal pro Woche Süssgetränke konsumieren, stieg von drei auf 18. Gründe die mit diesen Veränderungen in Zusammenhang stehen sind Preis, Geschmack, Produktangebot und Verfügbarkeit.Schlussfolgerung: Diese Ernährungsveränderungen könnten ernsthafte gesundheitliche Folgen nach sich ziehen. Hilfsmassnahmen, die den Vorschlägen der Studienteilnehmer Rechnung tragen, könnten problemlos eingeführt werden.

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Résumé. Changements alimentaires chez des réfugiés africains à Genève: une évaluation brève afin d’orienter des interventions nutritionnellesObjectifs: Evaluer les changements et problèmes alimentaires perçus par des réfugiés africains, dans le but de développer des interventions d’éducation nutritionnelle appropriées.Méthodes: Etude transversale qualitative au sein d’un échantillon de convenance. Les modifications de l’alimentation rapportées comme liées à la migration ont été recensées, groupées et comparées.Résultats: Dix-neuf interviews ont été analysées. Après la migration, les principaux changements alimentaires étaient la réduction du nombre de fruits et légumes différents consommés hebdomadairement de 10 à 2, et de 17 à 10 respectivement. Le nombre de répondants consommant des boissons sucrées plus de 3 fois par semaine est passé de 3 à 18. Des raisons de prix, de goût et d’accessibilité étaient évoquées pour expliquer ces changements.Conclusion: Ces changements alimentaires pourraient avoir des conséquences sanitaires sérieuses. Des interventions simples basées sur les suggestions des répondants devraient être envisagées.