Figure 3:
Schematic representation of the proposed mechanism involved in the inflammatory response, resident macrophage activation, mechanisms underlying the Inhibition of the contractile activity of the smooth muscle of the intestine following abdominal surgery and potential pharmacological targets. Intestinal manipulation and increased intestinal permeability results in the passage of bacteria and liposaccharides on the one hand and increased tissue degradation products on the other. Binding to TLRs results in activation of intracellular signals with increased transcription of pro-inflammatory genes and release of cytokines (TNFα, IL1β, IL6) and chemokines (MCP1, MIP1α), including upregulation of endothelial adhesion molecules such as ICAM1. This leads to an influx of leukocytes into the muscularis externa, followed by increased production of NO and PGs (via upregulation of iNOS and COX2) by resident macrophages and leukocytes, inhibiting contraction of intestinal smooth muscle. The secretion of ACh by enteric neurons, stimulated by vagal efferences, leads to activation of 7 αAChR receptors that inhibits TNF production.
Pharmacological targets:
Abbreviations:
TJ, tight junction; TLR, toll-like receptor; LPs, liposaccharide; 7αAChR α7-subtype of the nicotinic acetylcholine receptor; PAR2, proteinase-activated receptor-2; ICAM-1, intercellular adhesion molecule-1; LFA-1, lymphocyte function-associated antigen-1; MAP, Mitogen-activated protein; JNK, c-Jun N-terminal kinase; NF-kB, nuclear factor kB; STATS, signal transducers and activator of transcription; NO, nitric oxide; PGs, prostaglandin; Cox-2, cyclooxygenase 2 ; iNOS, inducible nitric oxide synthase; LFA-1, lymphocyte function-associated antigen-1.