Plos One
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Respiratory syncytial virus (RSV) bronchiolitis triggers a strong innate immune response characterized by excessive neutrophil infiltration which contributes to RSV induced pathology. The cytokine IL-17A enhances neutrophil infiltration into virus infected lungs. IL-17A is however best known as an effector of adaptive immune responses. ⋯ Various lung-resident lymphocytes produced IL-17A during early RSV infection in Balb/c mice, of which a local population of CD4 T cells stood out as the predominant RSV-induced cell type. By removing IL-17A during early RSV infection in mice we showed that IL-17A is responsible for enhanced innate neutrophil infiltration in vivo. Using patient material, in vitro studies, and an animal model of RSV infection, we thus show that early local IL-17A production in the airways during RSV bronchiolitis facilitates neutrophil recruitment with pathologic consequences to infant lungs.
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The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 (+/-) mice developed normally. ⋯ Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 (+/+) mice when fed HFD, were reduced in MCT1 (+/-) mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 (+/+) mice under high fat diet was prevented in the liver of MCT1 (+/-) mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet.
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Over-activation of the signal transducers and activators of the transcription 3 (Stat3) pathway in lung alveolar type II (AT II) epithelial cells induces chronic inflammation and adenocarcinoma in the lung of CCSP-rtTA/(tetO)7-CMV-Stat3C bitransgenic mice. One of Stat3 downstream genes products, chitinase 3-like 1 (CHI3L1) protein, showed increased concentration in both bronchioalveolar lavage fluid (BALF) and blood of doxycycline-treated CCSP-rtTA/(tetO)7-CMV-Stat3C bitransgenic mice. When tested in other inflammation-induced lung cancer mouse models, the CHI3L1 protein concentration was also highly increased in BALF and blood of these models with tumors. ⋯ Therefore, secretory CHI3L1 plays an important role in inflammation-induced lung cancer formation and potentially serve as a biomarker for lung cancer prediction. Based on our previous publication and this work, this is the first animal study linking overexpression of CHI3L1 to various lung tumor mouse models. These models will facilitate identification of additional biomarkers to predict and verify lung cancer under various pathogenic conditions, which normally cannot be done in humans.
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Previous studies have suggested that some pet dogs respond to their owners' hypoglycaemic state. Here, we show that trained glycaemia alert dogs placed with clients living with diabetes afford significant improvements to owner well-being. We investigated whether trained dogs reliably respond to their owners' hypoglycaemic state, and whether owners experience facilitated tightened glycaemic control, and wider psychosocial benefits. ⋯ HbA1C showed a small, non significant reduction after dog allocation. Based on owner-reported data we have shown, for the first time, that trained detection dogs perform above chance level. This study points to the potential value of alert dogs, for increasing glycaemic control, client independence and consequent quality of life and even reducing the costs of long-term health care.
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Laminae I-III of the spinal dorsal horn contain many inhibitory interneurons that use GABA and/or glycine as a neurotransmitter. Distinct neurochemical populations can be recognised among these cells, and these populations are likely to have differing roles in inhibiting pain or itch. Quantitative studies in rat have shown that inhibitory interneurons account for 25-40% of all neurons in this region. ⋯ As in the rat, the sst2A receptor is only expressed by inhibitory interneurons in laminae I-II, and is present on just over half (54%) of these cells. Antibody against the neurokinin 1 receptor was used to define lamina I, and we found that although the receptor was concentrated in this lamina, it was expressed by many fewer cells than in the rat. By estimating the total numbers of neurons in each of these laminae in the L4 segment of the mouse, we show that there are around half as many neurons in each lamina as are present in the corresponding segment of the rat.