Rodrigues, Anna C. Z.; Messi, Maria L.; Wang, Zhong‐Min; Abba, Martin C.; Pereyra, Andrea; Birbrair, Alexander; Zhang, Tan; O’Meara, Meaghan; Kwan, Ping; Lopez, Elsa I. S.; Willis, Monte S.; Mintz, Akiva; Files, D. Clark; Furdui, Cristina; Oppenheim, Ronald W.; Delbono, Osvaldo
doi: 10.1111/apha.13195pmid: 30269419
Fiorenza, Matteo; Gunnarsson, Thomas P.; Ehlers, Thomas S.; Bangsbo, Jens
doi: 10.1111/apha.13208pmid: 30339318
Winje, Ivan Myhre; Sheng, Xia; Hansson, Kenth‐Arne; Solbrå, Andreas; Tennøe, Simen; Saatcioglu, Fahri; Bruusgaard, Jo Christiansen; Gundersen, Kristian
doi: 10.1111/apha.13204pmid: 30325108
Hu, Qiongyuan; Knight, Patrick H.; Ren, Yanhan; Ren, Huajian; Zheng, Jiashuo; Wu, Xiuwen; Ren, Jianan; Sawyer, Robert G.
doi: 10.1111/apha.13194pmid: 30269441
Stimulator of interferons genes (STING) is an adaptor protein that plays a critical role in the secretion of type I interferons and pro‐inflammatory cytokines in response to cytosolic nucleic acid. Recent research indicates the involvement of the STING pathway in uncontrolled inflammation, sepsis, and shock. STING signaling is significantly up‐regulated in human sepsis, and STING agonists are suggested to contribute to the pathogenesis of sepsis and shock. Nevertheless, little is known about the consequences of activated STING‐mediated signaling during sepsis. It has been shown that aberrant activation of the STING‐dependent way can result in increased inflammation, type I interferons responses, and cell death (including apoptosis, necroptosis, and pyroptosis). In addition, autophagy modulation has been demonstrated to protect against multiple organs injuries in animal sepsis model. However, impaired autophagy may contribute to the aberrant activation of STING signaling, leading to uncontrolled inflammation and cell death. Here we present a comprehensive review of recent advances in the understanding of STING signaling, focusing on the regulatory mechanisms and the roles of this pathway in sepsis.
Meroni, Elisa; Stakenborg, Nathalie; Viola, Maria Francesca; Boeckxstaens, Guy E.
doi: 10.1111/apha.13163pmid: 29998613
Over the past decades, there has been an increasing understanding of cellular and molecular mechanisms that mediate modulation of the immune system by the autonomic nervous system. The discovery that vagal nerve stimulation (VNS) attenuates endotoxin‐induced experimental sepsis paved the way for further studies investigating neuro‐immune interaction. In particular, great attention is now given to intestinal macrophages: several studies report the existence of both intrinsic and extrinsic neural mechanisms by which intestinal immune homoeostasis can be regulated in different layers of the intestine, mainly by affecting macrophage activation through neurotransmitter release. Given the important role of inflammation in numerous disease processes, such as inflammatory bowel disease (IBD), cholinergic anti‐inflammatory mechanisms are under intense investigation both from a basic and clinical science perspective in immune‐mediated diseases such as IBD. This review discusses recent insights on the cross‐talk between enteric neurons and the immune system, especially focusing on macrophages, and provides an overview of basic and translational aspects of the cholinergic anti‐inflammatory response as therapeutic alternative to reinstall immune homoeostasis in intestinal chronic inflammation.
Curry, Fitz‐Roy E.; Taxt, Torfinn; Rygh, Cecilie Brekke; Pavlin, Tina; Bjønrstad, Ronja; Døskeland, Stein Ove; Reed, Rolf K.
doi: 10.1111/apha.13199pmid: 30300965
doi: 10.1111/apha.13196pmid: 30288889
Despite substantial progress made towards a better understanding of the importance of skeletal muscle K+ regulation for human physical function and its association with several disease states (eg type‐II diabetes and hypertension), the molecular basis underpinning adaptations in K+ regulation to various stimuli, including exercise training, remains inadequately explored in humans. In this review, the molecular mechanisms essential for enhancing skeletal muscle K+ regulation and its key determinants, including Na+,K+‐ATPase function and expression, by exercise training are examined. Special attention is paid to the following molecular stressors and signaling proteins: oxygenation, redox balance, hypoxia, reactive oxygen species, antioxidant function, Na+,K+, and Ca2+ concentrations, anaerobic ATP turnover, AMPK, lactate, and mRNA expression. On this basis, an update on the effects of different types of exercise training on K+ regulation in humans is provided, focusing on recent discoveries about the muscle fibre‐type‐dependent regulation of Na+,K+‐ATPase‐isoform expression. Furthermore, with special emphasis on blood‐flow‐restricted exercise as an exemplary model to modulate the key molecular mechanisms identified, it is discussed how training interventions may be designed to maximize improvements in K+ regulation in humans. The novel insights gained from this review may help us to better understand how exercise training and other strategies, such as pharmacological interventions, may be best designed to enhance K+ regulation and thus the physical function in humans.
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