Irisin, an adipomiokine known as a mediator of physical activity, induces the browning of adipose tissue and it has potentially protective properties in the development of obesity-related states, such as insulin resistance, arteriosclerosis, and type 2 diabetes. Despite numerous studies conducted on this factor, still little is known about its impact on the functioning of immunocompetent cells, but its potential anti-inflammatory properties were previously suggested. In the current study we investigated the role of irisin (0–100 nM) in the downstream pathway activation of Toll-like receptor 4 (TLR4) in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS; 100 ng/mL). The results have shown that irisin in high concentrations (50, 100 nM) significantly decreased the TLR4 and MyD88 protein levels, as well as the phosphorylation of nuclear factor-κB (NF-κB), consequently leading to the reduction in the release of crucial pro-inflammatory cytokines. The above was confirmed for interleukin 1β (IL-1β), tumor necrosis factor α (TNFα), interleukin 6 (IL-6), keratinocyte chemoattractant (KC), monocyte chemotactic protein 1 (MCP-1), as well as for high mobility group box 1 (HMGB1). Moreover, our results indicate that this effect is connected with irisin’s impact on the phosphorylation of mitogen-activated protein kinases (MAPKs), where a significant reduction in p-JNK and p-ERK but not p-p38 was observed. In conclusion, these data suggest that irisin has potentially anti-inflammatory properties connected with the downregulation of downstream pathways of TLR4/MyD88.

Over the past few years, the role of intestinal alkaline phosphatase (IAP) as a crucial mucosal defence factor essential for maintaining gut homeostasis has been established. IAP is an important apical brush border enzyme expressed throughout the gastrointestinal tract and secreted both into the intestinal lumen and into the bloodstream. IAP exerts its effects through dephosphorylation of proinflammatory molecules including lipopolysaccharide (LPS), flagellin, and adenosine triphosphate (ATP) released from cells during stressful events. Diminished activity of IAP could increase the risk of disease through changes in the microbiome, intestinal inflammation, and intestinal permeability. Exogenous IAP exerts a protective effect against intestinal and systemic inflammation in a variety of diseases and represents a potential therapeutic agent in diseases driven by gut barrier dysfunction such as IBD. The intestinal protective mechanisms are impaired in IBD patients due to lower synthesis and activity of endogenous IAP, but the pathomechanism of this enzyme deficiency remains unclear. IAP has been safely administered to humans and the human recombinant form of IAP has been developed. This review was designed to provide an update in recent research on the involvement of IAP in intestinal inflammatory processes with focus on IBD in experimental animal models and human patients.

BackgroundStress of different origin is known to alter so called “brain-gut axis” and contributes to a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases. The stressful situations and various stressors including psychosocial events, heat, hypo- and hyperthermia may worsen the course of IBD via unknown mechanism. The aims of this paper were to provide an overview of experimental and clinical evidences that stress activates the brain-gut axis which results in a mucosal mast cells activation and an increase in the production of proinflammatory cytokines and other endocrine and humoral mediators.MethodsResearch and online content related to effects of stress on lower bowel disorders are reviewed and most important mechanisms are delineated.ResultsBrain conveys the neural, endocrine and circulatory messages to the gut via brain-gut axis reflecting changes in corticotrophin releasing hormone, mast cells activity, neurotransmission at the autonomic nerves system and intestinal barrier function all affecting the pathogenesis of animal colitis and human IBD. Stress triggers the hypothalamus-pituitary axis and the activation of the autonomic nervous system, an increase in cortisol levels and proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-8, interleukin-1beta and interleukin-6.ConclusionThe acute or chronic stress enhances the intestinal permeability weakening of the tight junctions and increasing bacterial translocation into the intestinal wall. An increased microbial load in the colonic tissue, excessive cytokine release and a partially blunted immune reactivity in response to stress result in its negative impact on IBD.

Sedentary life style is considered to be an independent risk factor for many disorders, including development of type 2 diabetes, obesity, immune dysfunction, asthma, and neurological or coronary heart disease. Irisin is released from myocytes during physical activity, and acts as a link between muscles and other tissues and organs. This myokine is produced as a result of proteolytic cleavage of FNDC5 protein present in the membrane of myocytes. Secretion of irisin is regulated by N-linked oligosaccharides attached to the protein molecule. The two N-glycan molecules, which constitute a significant part of the irisin glycoprotein, regulate the browning of adipocytes, which is the most important function of irisin. A receptor specific for irisin has still not been discovered. In some tissues irisin probably acts via integrins, which are widely expressed transmembrane receptors. Many studies have confirmed the multifunctional role of irisin and the beneficial effects of this molecule on body homeostasis. Irisin reduces systemic inflammation, maintains the balance between resorption and bone formation, and modulates metabolic processes and the functioning of the nervous system. It suppresses the expression and release of pro-inflammatory cytokines in obese individuals and attenuates inflammation in adipose tissue. The impact of irisin on cancer cell proliferation, migration, and invasion has also been demonstrated in numerous studies, which proves its role in carcinogenesis. Owing to these pleiotropic and beneficial properties, irisin may be a potential option to prevent and treat civilization-related diseases which are, nowadays, considered to be the major health problems in Western societies.

We reviewed and analyzed the relationship between physical exercise and inflammatory bowel disease (IBD) which covers a group of chronic, relapsing, and remitting intestinal disorders including Crohn's disease (CD) and ulcerative colitis. The etiology of IBD likely involves a combination of genetic predisposition and environmental risk factors. Physical training has been suggested to be protective against the onset of IBD, but there are inconsistencies in the findings of the published literature. Hypertrophy of the mesenteric white adipose tissue (mWAT) is recognized as a characteristic feature of CD, but its importance for the perpetuation of onset of this intestinal disease is unknown. Adipocytes synthesize proinflammatory and anti-inflammatory cytokines. Hypertrophy of mWAT could play a role as a barrier to the inflammatory process, but recent data suggest that deregulation of adipokine secretion is involved in the pathogenesis of CD. Adipocytokines and macrophage mediators perpetuate the intestinal inflammatory process, leading to mucosal ulcerations along the mesenteric border, a typical feature of CD. Contracting skeletal muscles release biologically active myokines, known to exert the direct anti-inflammatory effects, and inhibit the release of proinflammatory mediators from visceral fat. Further research is required to confirm these observations and establish exercise regimes for IBD patients.