Downregulation of deubiquitinating enzyme USP25 promotes the development of allergic rhinitis by enhancing TSLP signaling in the nasal epithelium.

Ubiquitin­specific peptidase 25 (USP25) is a key deubiquitylase belonging to the USP superfamily that is primarily involved in inflammation and the immune response. Thymic stromal lymphopoietin (TSLP) is an epithelial­derived cytokine that is regarded as the master switch that initiates and maintains the type 2 immune response in allergic rhinitis (AR). However, the molecular mechanisms by which USP25 regulates TSLP signaling in the nasal epithelium in AR remain unclear. The present study assessed the protein expression levels of USP25 in the nasal epithelium of patients with AR. Moreover, USP25 knockout (KO) and wild­type (WT) mice were treated with ovalbumin (OVA) to establish a model of AR. The results of western blotting and immunohistochemistry in the present study demonstrated that the protein expression levels of USP25 were significantly decreased in the nasal mucosa of patients with AR and AR mice, whereas the protein expression levels of TSLP were significantly increased. Allergic inflammation was more severe in USP25 KO mice compared with WT mice exposed to OVA, as demonstrated by increased nose scratching and sneezing, increased eosinophil infiltration, goblet cell hyperplasia and enhanced T helper type 2 (Th2) cytokine production. The results of in vitro experiments demonstrated that silencing or overexpression of USP25 decreased or increased TNF receptor­associated factor 3 (TRAF3) protein expression levels, respectively, in human nasal epithelial cells, whereas TSLP protein expression levels were negatively associated with the expression of USP25 and TRAF3. In summary, USP25 downregulation enhanced TSLP signaling in the nasal mucosal epithelium via decreased TRAF3 expression, thereby exacerbating inflammation in AR. Therefore, USP25 may act as a novel therapeutic target in AR.

miR-31 attenuates murine allergic rhinitis by suppressing interleukin-13-induced nasal epithelial inflammatory responses.

The present study aimed to investigate whether microRNA (miR)­31 exerted therapeutic potential in allergic rhinitis (AR) and to explore its underlying mechanism. Firstly, the expression levels of miR­31 were detected by reverse transcription­quantitative PCR in the nasal mucosa of patients and mice. Subsequently, an ovalbumin (OVA)­induced animal model of AR was constructed. Allergic symptom score, histopathological characteristics, OVA­specific immunoglobulin E (IgE) titers, and T­helper (Th)1 and Th2 cell­related cytokine levels were analyzed in OVA­sensitized mice, miR­31­overexpressing mice, miR­negative control mice and control mice. Furthermore, interleukin (IL)­13­stimulated nasal epithelial cells (NECs) were used to assess the effects of miR­31 on the production of IL­13­induced inflammatory cytokines and mucin 5AC by performing western blotting and ELISA. The expression levels of miR­31 were significantly decreased in the nasal mucosa of the AR group compared with those in the control group. Moreover, upregulation of miR­31 markedly attenuated sneezing and nasal rubbing events, reduced nasal eosinophil infiltration and goblet cell hyperplasia, and decreased the levels of OVA­specific IgE and Th2­related cytokines. In addition, subsequent in vitro experiments showed that upregulation of miR­31 inhibited IL­13 receptor α1 chain expression and signal transducer and activator of transcription 6 phosphorylation in NECs. Furthermore, miR­31 suppressed IL­13­induced expression of thymic stromal lymphopoietin, granulocyte­macrophage colony­stimulating factor, eotaxin and mucin 5AC in NECs. In conclusion, these data revealed that miR­31 could ameliorate AR by suppressing IL­13­induced nasal epithelial inflammatory responses, and thus may serve as a novel therapeutic target for AR.

Negative pressure wound therapy promotes wound healing by suppressing macrophage inflammation in diabetic ulcers.

Aim: This work aims to explore the biological role of negative pressure wound therapy (NPWT) in the treatment of diabetic ulcer. Materials & methods: Full-thickness skin defects were created in diabetic (db/db) and non diabetic (db/m) mice to create wound models. The mice were received NPWT or rapamycin injection. Mouse macrophage cells (Raw264.7) were treated with lipopolysaccharide to induce inflammatory response, and then received negative pressure treatment. We observed the wound healing of mice and examined gene and protein expression and CD68+ macrophage levels. Results: NPWT notably enhanced the wound closure ratio, and inhibited the LC3-II/LC3-I ratio and Beclin-1 expression in diabetes mellitus (DM) mice. NPWT decreased CD68+ macrophage levels in wound tissues of DM mice. The influence conferred by NPWT was abolished by rapamycin treatment. Negative pressure repressed the LC3-II/LC3-I ratio and the expression of Beclin-1, TNF-α, IL-6 and IL-1ß in the Raw264.7 cells. Conclusion: NPWT promotes wound healing by suppressing autophagy and macrophage inflammation in DM.