Our results suggest
that among many other mediators of eicosanoid signalling n-butyrate massively induces PGE2 production by increasing the expression of PTGS2 (COX-2) in monocytes following TLR4 and TLR2 activation and induces secretion of LTB4 and thromboxane B2. This underscores the role of n-butyrate as a crucial mediator of gut-specific immunity. Despite continuous exposure to antigens, gastrointestinal immunity normally guarantees mucosal welfare, differentiating Cabozantinib between potential pathogens and the commensal flora. In case of disturbance, intestinal homeostasis becomes dysbalanced and, for example, inflammatory bowel disease can ensue. The extensive and dynamic interactions between the symbionts and the immune
system are key to colonic homeostasis and health, and require tight regulation of pro-inflammatory and anti-inflammatory immune reactions. Several types of immune cells, as well as the inimitable specific environment are involved in the establishment of this particular system;[1] however, little is known about specific factors that guide the establishment of this unique local environment. Short-chain fatty acids (SCFAs), like acetate, propionate or n-butyrate, are organic acids produced in the gut by the resident colonic microflora through breakdown of carbohydrates.[1, 2] The production of SCFAs check details by bacterial fermentation also allows the supply of energy from dietary fibre that is not digested in the small intestine. ID-8 It has been estimated that SCFAs might contribute up to 15% of the total caloric requirements of the human body. Furthermore, SCFAs are pivotal for maintaining mucosal homeostasis in the gastrointestinal tract.[3-6] n-Butyrate exerts multiple biological effects on a variety of cell types leading to immune modulation, cell cycle inhibition, induction of programmed cell death and cellular differentiation. It potently regulates inflammatory reactions by modulating cytokine production, kinase activity and transcription factors in various immune cell populations.[7, 8] Hence, it has been shown that n-butyrate differentially
affects pro-inflammatory and anti-inflammatory cytokine production.[8] Furthermore, n-butyrate prevents lipopolysaccharide (LPS) -induced maturation of dendritic cells, resulting in a reduced capability to stimulate T cells.[9] Many of the effects of n-butyrate are attributed to inhibition of histone deacetylation and of nuclear factor-κB (NF-κB) transactivation; however, the complete spectrum of the molecular mode of actions responsible for the immunomodulatory effects of this SCFA is still not fully elucidated. Originally recognized for their potential to govern vascular homeostasis and platelet aggregation, eicosanoids like prostaglandins (PGs) and leukotrienes (LTs) have also been implicated in several immunopathological processes, like inflammation, allergy and autoimmune diseases, as well as in cancer.