MicroRNA-146a negatively regulates IL-33 in activated group 2 innate lymphoid cells by inhibiting IRAK1 and TRAF6.

Type II innate lymphoid cells (ILC2) play a very important role in the pathogenesis of allergic asthma. This study aims to investigate whether miR-146a inhibition of asthma is related with interleukin (IL)-33 signaling path way in ILC2 and the underlying mechanisms. Asthma mice model was induced by ovalbumin. miRNA146a mimics was administrated to asthma mice or transfected to activated ILC2 purified from asthma mice lung. RT-PCR was used to detect miRNA146a level in lung tissue and ILC2. IL-5 and IL-13 levels in culture supernatant were detected by flow cytometry. Interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), signal transducer and activator of transcription 1 (STAT1) protein expression levels were detected by western blot. miR-146a directly inhibited ILC2 function and suppressed ILC2 proliferation both in vivo and in vitro. During stimulation of ILC2, miR-146a expression gradually increased with a decrease of cell proliferation. Modulation of ILC2 function by miR-146a may depend on IL-33/interleukin 1 receptor-like 1 (IL1RL1 or ST2) signaling through inhibiting IRAK1 and TRAF6.miR-146a can inhibit IRAK1 and TRAF6, downstream molecules of ST2 signal pathway, thereby negatively regulate IL-33/ST2-activated ILC2 to inhibit asthma. Targeting miR-146 maybe a novel strategy for the treatment of allergic asthma.

Systemic treatment with resveratrol alleviates adjuvant arthritis-interstitial lung disease in rats via modulation of JAK/STAT/RANKL signaling pathway.

Interstitial lung disease (ILD) is the most common pulmonary manifestation of Rheumatoid arthritis (RA) lung disease. The mechanism of RA-ILD remains obscure and more effective treatments are still needed. Resveratrol (RSV) a phytoalexin found with anti-inflammation and antioxidant activity. RSV has been reported to protect against RA. In current study, we evaluated the effects of RSV on RA-ILD and further explored the underlying mechanisms. We established the RA-ILD rat model by injecting Freund's complete adjuvant (FCA). After administration of RSV into RA-ILD rats, the disease parameters were assessed, inflammatory cytokines productions were analyzed, and the effects of RSV on JAK/STAT/RANKL were evaluated. Injection of FCA caused RA-ILD in rats, which had clear lung damage, fibrosis, and elevated pro-inflammatory cytokines in both serum and lung. RSV treatment significantly ameliorated the lung disease and prevented pro-inflammatory cytokines production. In addition, RSV inhibited JAK/STAT/RANKL signaling pathway in RA-ILD rats. RSV treatment alleviates RA-ILD in rats by inhibiting JAK/STAT/RANKL signaling pathway.

Mir-5100 Mediates Proliferation, Migration and Invasion of Oral Squamous Cell Carcinoma Cells Via Targeting SCAI.

PURPOSE: We aimed to investigate the role of microRNA-5100 (miRNA-5100) in oral squamous cell carcinoma (OSCC) and its underlying mechanisms.Material/Methods: The expression of miR-5100 and suppressor of cancer cell invasion (SCAI) in OSCC cell lines were examined. A luciferase reporter assay was applied to confirm the combination between miR-5100 and SCAI. Then, miR-5100 inhibitor or small hairpin RNA (shRNA)-SCAI were transfected into cells. Cell Counting Kit-8 assay was executed for testing cell proliferation ability. Flow cytometry assay was exploited for measuring cell cycle. Invasion and migration of OSCC cells were assessed using Transwell assay and wound healing assay. The expression of proteins were detected using western blotting. RESULTS: The results demonstrated that the level of miR-5100 was upregulated while SCAI was downregulated in OSCC cells. SCAI was verified as a direct target of miR-5100. MiR-5100 silencing suppressed proliferation of OSCC cells, increased cells in the G1 and G2 phases, and reduced those in the S phase, which was reversed after transfection with shRNA-SCAI. Moreover, miR-5100 inhibitor downregulated the expression of cyclin-dependent kinase-2 (CDK-2) and cyclinD1, accompanied by upregulation in p27 expression, whereas SCAI silencing had the opposite results. The invasion and migration abilities of OSCC cells were reduced after treatment with miR-5100 inhibitor, whereas SCAI silencing suppressed the effects of miR-5100 inhibitor on OSCC cell behaviors. CONCLUSION: These findings suggested that miR-5100 silencing inhibit proliferation, invasion and migration of OSCC cells via upregulating the expression of SCAI, which provides theoretical basis and treatment strategies for the treatment of OSCC.