IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.
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IL-17F plays a crucial role in airway inflammatory diseases including asthma, but its function has not been fully elucidated. CCL20 is also involved in allergic airway inflammation, while its regulatory mechanisms remain to be defined. To further identify a novel role of IL-17F, the expression of CCL20 by IL-17F in bronchial epithelial cells and the signaling mechanisms involved were investigated. Bronchial epithelial cells were stimulated with IL-17F, and the levels of CCL20 gene and protein measured, with the effects of the addition of various kinase inhibitors and siRNAs also investigated. IL-17F significantly induced the expression of CCL20 gene and protein. Pretreatment with inhibitors for MEK1/2, Raf1 and MSK1, and overexpression of a Raf1 dominant-negative mutant significantly diminished IL-17F-induced CCL20 production. Moreover, transfection of the siRNAs targeting MSK1, p90RSK, and CREB blocked CCL20 expression. These findings suggest that IL-17F is able to induce CCL20 via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. The IL-17F/CCL20 axis may be a novel pharmacological target for asthma.
In order to improve the outcome, detection of early stage lung cancer in patients with good PS and thorough pretreatment evaluation for appropriate treatment are indeed essential even for the > or =80 age group of patients.
Abstract. The aim of the present study was to investigate the effect of rikkunshi-to, a Japanese herbal medicine, on post-chemotherapeutic appetite loss. Patients with unresectable lung cancer, who were treated with carboplatin (CBDCA)-containing, cisplatin (CDDP)-containing or non-platinum chemotherapy between 2011 and 2014, were recruited for the prospective study. For each course of chemotherapy, the patients were randomized into two groups, with or without a rikkunshi-to prescription. In patients treated with CBDCA-containing chemotherapy, food intake at day 7 following the initiation of chemotherapy in the rikkunshi-to treatment group was significantly higher compared with the group not treated with rikkunshi-to (P=0.0078). However, a significant improvement in food intake with rikkunshi-to treatment was not observed in the CDDP-containing and non-platinum chemotherapy groups. An improved assessment of the incidence rate of chemotherapy-induced appetite loss is essential for achieving adequate control. The results of the present study indicated the possibility of the clinical application of rikkunshi-to for improving post-chemotherapeutic appetite loss.
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