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.

[Experimental study of the effects on proliferation and apoptosis of A549 cell line of adenocarcinoma of the lung with compatibility of Radix ex Rhizoma ginseng and Fafces Trogopterori].

OBJECTIVE: To observe the effects of the compatibility of Radix ex Rhizoma Ginseng and Fafces Trogopterori on proliferation and apoptosis of A549 cell line of adenocarcinoma of the lung, to clarify the mechanism, to explore the best proportion compatibility, and to offer the reasonable experiment evidence in clinical medicine therapy. METHOD: Twenty-five healthy Wistar rats were divided into five groups randomly, 5 rats in each group, including normal group, Radix ex Rhizoma Ginseng and Fafces Trogopterori in the ratio of 1:1 group, 1:2 group, 2:1 group, and complex recipe of beetle capsule group. After the pharmacy liquor was decocted, equivalent dose for rat was calculated. According to the weights, all rats were intragastric administrated at the standard of 1 mL x 100 g(-1), twice a day, continuously for 3 days. One hour after the last administration, the serum was collected and mixed with culture media RPMI 1640 to prepare the drug serum incubation liquid at the concentration of 10%. MTT was used to measure the growth curve and the inhibition rate of tumor cell, and the apoptosis was observed by electron microscope. RESULT: The compatibility of Radix ex Rhizoma Ginseng and Fafces Trogopterori could inhibit the cell proliferation of cell line A549 of lung adenocarcinoma and have an inducement on apoptosis. The effect was significant in the ratio of 2:1. CONCLUSION: These results indicate that inhibiting the proliferation and inducing the apoptosis of tumor cell may be one of the anticancer mechanism of the compatibility of Radix ex Rhizoma Ginseng and Fafces Trogopterori.