TNF-α promotes CXCL-1/8 production in keratinocytes by downregulating galectin-3 through NF-κB and hsa-miR-27a-3p pathway to contribute psoriasis development.

OBJECTIVE: Treatment with TNF-α inhibitors improve psoriasis with minimize/minor neutrophils infiltration and CXCL-1/8 expression in psoriatic lesions. However, the fine mechanism of TNF-α initiating psoriatic inflammation by tuning keratinocytes is unclear. Our previous research identified the deficiency of intracellular galectin-3 was sufficient to promote psoriasis inflammation characterized by neutrophil accumulation. This study aims to investigate whether TNF-α participated in psoriasis development through dysregulating galectin-3 expression. METHODS: mRNA levels were assessed through quantitative real-time PCR. Flow cytometry was used to detect cell cycle/apoptosis. Western blot was used to evaluate the activation of the NF-κB signaling pathway. HE staining and immunochemistry were used to detect epidermal thickness and MPO expression, respectively. Specific small interfering RNA (siRNA) was used to knock down hsa-miR-27a-3p while plasmids transfection was used to overexpress galectin-3. Further, the multiMiR R package was utilized to predict microRNA-target interaction. RESULTS AND DISCUSSION: We found that TNF-α stimulation altered cell proliferation and differentiation and promoted the production of psoriasis-related inflammatory mediators along with the inhibition of galectin-3 expression in keratinocytes. Supplement of galectin-3 could counteract the rise of CXCL-1/8 but not the other phenotypes of keratinocytes induced by TNF-α. Mechanistically, inhibition of the NF-κB signaling pathway could counteract the decrease of galectin-3 and the increase of hsa-miR-27a-3p expression whereas silence of hsa-miR-27a-3p could counteract the decrease of galectin-3 expression induced by TNF-α treatment in keratinocytes. Intradermal injection of murine anti-CXCL-2 antibody greatly alleviated imiquimod-induced psoriasis-like dermatitis. CONCLUSION: TNF-α initiates psoriatic inflammation by increasing CXCL-1/8 in keratinocytes mediated by the axis of NF-κB-hsa-miR-27a-3p-galectin-3 pathway.

Efficacy and safety of Run Zao Zhi Yang capsule on chronic eczema: a multiple-center, randomized, double-blind, placebo-controlled clinical study.

Background: Run Zao Zhi Yang capsule (RZZYC) has been widely applied for eczema treatment as a traditional Chinese medicine, while its efficacy has not been scientifically investigated. Objective: We conducted this multiple-centers, randomized, double-blind, placebo-controlled study to investigate the effectiveness and safety of RZZYC on the treatment of patients with mild to moderate chronic eczema. Methods: 240 patients were randomly assigned into the experimental group and the placebo group. The primary efficacy indicator was the Eczama Area and Severity Index (EASI) score at week 4. The patient with an EASI score that decreases more than 95% from baseline (EASI 95) was judged as cured. The cured patients were followed up for another 8 weeks. The differences on EASI, Visual Analogue Score (VAS), and Dermatology Life Quality Index (DLQI) score were compared. Results: The proportions of EASI 95 and EASI 60 in the experimental group were significantly higher than those of the control group at week4 (p = .002 and p < .001, respectively), the VAS score decreased more significantly in the experimental group at week 4. After 8 weeks follow-up, no difference on recurrence rate and adverse event rate between the two groups was observed. Conclusion: RZZYC provides a good effect on the treatment of mild-to-moderate chronic eczema with a low recurrence and tolerable adverse events, and is a potential treatment that may be implemented in clinical practice.