Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC gene expression via the inhibition of Gαq-induced Ca2+ signaling. IL-1ra inhibited IL-1α protein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1α secretion were both mediated by PLCβ3. A dominant-negative mutation in the PDZ-binding domain of PLCβ3 inhibited ATP/P2Y2-induced IL-1ra and IL-1α secretion. IL-1α in the presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2 complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through inhibition of IL-1α secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.

BackgroundPostoperative body temperature is closely associated with prognosis although there is limited research regarding this association at Postoperative intensive care unit (ICU) admission. Furthermore, no studies have used digital axillary thermometers to measure Postoperative body temperature. This study investigated the association between mortality and Postoperative temperature measured using a digital axillary thermometer within 10 minutes after ICU admission. MethodsThis retrospective observational study evaluated data from adult patients admitted to an ICU after elective or emergency surgery. The primary outcome was 1-year mortality after ICU admission. Multivariable logistic regression analysis with restricted cubic splines was used to evaluate the association between temperature and outcomes. ResultsWe evaluated data from 5,868 patients admitted between January 1, 2013 and May 31, 2016, including 5,311 patients (90.5%) who underwent noncardiovascular surgery and 557 patients (9.5%) who underwent cardiovascular surgery. Deviation from the median temperature (36.6℃) was associated with increases in 1-year mortality (≤ 36.6℃: linear coefficient, –0.531; P<0.001 and ≥36.6℃: spline coefficient, 0.756; P<0.001). Similar statistically significant results were observed in the noncardiovascular surgery group, but not in the cardiovascular surgery group. ConclusionsAn increase or decrease in body temperature (vs. 36.6℃) measured using digital axillary thermometers within 10 minutes of Postoperative ICU admission was associated with increased 1-year mortality. However, no significant association was observed after cardiovascular surgery. These results suggest that Postoperative temperature is associated with longterm mortality in patients admitted to the surgical ICU in the Postoperative period.

Enhancer is a regulatory element that enhances the transcription of target gene. 1,2 Transcription factors and coactivators bind to active enhancers and histones are depleted from them in a chromatin context. Enhancers cause active histone modifications, such as H3K27ac and H3K4me2/3, across the gene locus and physically interact with target promoters. It has been reported that enhancers affect chromatin interactions among other enhancers, target genes, and neighboring CTCF sites. [3][4][5]

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Pseudomonas aeruginosa is a Gram-negative bacterial pathogen related to a wide range of infections including lung disease. 1,2 Because of its metabolic flexibility and fundamental resistance to antimicrobials, P. aeruginosa grows well in a wide variety of materials and environments, including in-hospital facilities and patient devices. 3 Although it rarely infects healthy individuals, it is a leading and wellknown opportunistic pathogen, especially in immunocompromised patients with defective immune defences. 4 P. aeruginosa is known to colonize and infect the lungs of patients with cystic fibrosis (CF) and advanced stages of chronic obstructive pulmonary disease (COPD). 5,6 Most importantly, P. aeruginosa has multiple antibiotic resistance and tolerance that allow it to survive antibiotic treatment