[55] Leukotrienes are synthesized in response to a large spectrum of various infectious agents and enhance the capacity of macrophages and other immune cells to ingest and kill microbes and to produce antimicrobial mediators. In animal models of infection, genetic or pharmacological interference with leukotriene synthesis or signalling massively impairs local microbial clearance.[56] In summary,

these data imply that see more certain levels of leukotrienes are indispensable to control microbial invaders and to maintain local immune reactivity not only in the lung but also in the gastrointestinal tract. Similar to prostanoids, the SCFA n-butyrate brings about interference with immune cell activation at key stages of immune cell activation inhibiting dendritic cell maturation and consequent T-cell actions. Previous studies demonstrated that pre-treatment of human peripheral blood mononuclear cells or monocytes as well as monocyte-derived dendritic cells with this agent resulted in a dose- and time-dependent down-regulation

of their capability to stimulate T-cell responses.[8, 9, 22, 56-61] Therefore, it is tempting to speculate that n-butyrate itself, or through induction of mediators like eicosanoids, may contribute to the generation of an anti-inflammatory immune responsiveness. As the presence of n-butyrate is largely restricted to the gastrointestinal tract and immunological Teicoplanin features of this region have striking similarities to the effects brought about by KU-60019 chemical structure this physiologically occurring substance, further elucidation of the underlying principles appears

promising. There are several potential transcriptional regulatory elements in the promotor region of the COX-2 gene including a peroxisome proliferator response element, two cAMP response elements, a sterol response element, two NF-κB sites, an SP1 site, a CAAT enhancer binding protein motif, two AP-2 sites, an E-box, and a Tata box.[63] Previous studies have shown that cAMP response element-binding protein (CREB) and NF-κB are particularly important in LPS-induced COX-2 transcription indicating that p65/p50 heterodimer together with CREB is required for an early phase of rapid induction and the p50 homodimer together with CREB is crucial during later phases.[63] Testing the impact of n-butyrate treatment on LPS triggering, we found that the early phase of NF-κB signalling including IκB phosphorylation, IκB degradation and phosphorylation of p65 and p50 was completely unaffected. The late phase of the classical NF-κB pathway, as indicated by p65/p50 DNA binding, however, was profoundly inhibited. These finding are in agreement with previous studies[25, 64-66] showing inhibition of NF-κB signalling by n-butyrate. Furthermore, we were able to demonstrate that phosporylation of p105, the precursor for the formation of p50 homodimer, was also sustained.