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Asthma is a chronic airway inflammation in which Th2 and Th17 cells play critical roles in its pathogenesis. We have reported that atypical protein kinase (PKC) λ/ι is a new regulator for Th2 differentiation and function. However, the role of PKCλ/ι for Th17 cells remains elusive. In this study, we explored the effect of PKCλ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional PKCλ/ι-deficient mice. Our findings indicate that PKCλ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKCλ/ι-deficiency was associated with the downregulation of Stat3 and Rorγt, key Th17 transcription factors. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of house dust mites. PKCλ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional PKCλ/ι-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, PKCλ/ι emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The "hygiene hypothesis" is a theory try to explain the dramatic increases in the prevalence of autoimmune and allergic diseases over the past two to three decades in developed countries. According to this theory, reduced exposure to parasites and microorganisms in childhood is the main cause for the increased incidences of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. In this study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found that S. japonicum infection downregulated airway hyperresponsiveness. The infiltrating cells, Th17 and Th2 effector cytokines in the bronchoalveolar lavage (BAL) fluids and lungs were significantly reduced in the infected mice. Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection. To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms.

Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota. [ABSTRACT FROM AUTHOR]

Selenium (Se) is vital for health because of its antioxidative and anti-inflammation functions. The aim of this study was to determine if dietary selenium could inhibit the rat lung injury induced by ambient fine particulate matter (PM). Sprague-Dawley rats were randomly allocated in seven groups ( n = 8). The rats in PM exposure group were intratracheally instilled with 40 mg/kg of body weight (b.w.) of PM suspension. The rats in Se prevention groups were pretreated with 17.5, 35, or 70 μg/kg b.w. of Se for 4 weeks, respectively. Then, the rats were exposed to 40 mg/kg b.w. of PM in the fifth week. The bronchoalveolar lavage fluid (BALF) was collected to count the neutrophil numbers and to analyze the cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), soluble intercellular adhesion molecule-1 (sICAM-1)) related to inflammation, the markers related to oxidative stress (total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA)), and the indicators related to cell damage (lactate dehydrogenase (LDH), total protein (TP), alkaline phosphatase (AKP)). The lung lobe that has not undergone bronchoalveolar lavage was processed for light microscopic examination. The results showed that the proportions of neutrophils in the BALF and the pathologic scores of the lung in PM-exposed groups were higher than that in the control group ( P < 0.05). Se pretreatment caused a dose-dependent decrease in TNF-α, IL-1β, sICAM-1, LDH, TP, AKP, and MDA when compared with the PM-only exposure group. Meanwhile, the dose-dependent increase in T-AOC, T-SOD, and GSH-Px activities were observed in rats pretreated with Se. In conclusion, Se pretreatment may protect rat lungs against inflammation and oxidative stress induced by PM, which suggests that Se plays an important role as a kind of potential preventative agent to inhibit the PM-induced lung injury. [ABSTRACT FROM AUTHOR]

There is increasing controversy on whether acute exposure to ambient carbon monoxide (CO) is hazardous on respiratory health. We therefore performed a longitudinal panel study to evaluate the acute effects of ambient CO on fractional exhaled nitric oxide (FeNO), a well-established biomarker of airway inflammation. We completed 4–6 rounds of health examinations among 75 healthy young adults during April to June in 2013 in Shanghai, China. We applied the linear mixed-effect model to investigate the short-term associations between CO and FeNO. CO exposure during 2–72 h preceding health tests was significantly associated with decreased FeNO levels. For example, an interquartile range increase (0.3 mg/m 3 ) of 2-h CO exposure corresponded to 10.6% decrease in FeNO. This association remained when controlling for the concomitant exposure to co-pollutants. This study provided support that short-term exposure to ambient CO might be related with reduced levels of FeNO, a biomarker of lower airway inflammation. [ABSTRACT FROM AUTHOR]