title: Vanilloid receptor-1 regulates neurogenic inflammation in colon and protects mice from colon cancer.
abstract: Neuroinflammation driven by the vanilloid-type ion channel receptor transient receptor potential vanilloid type 1 (TRPV-1) is suspected to play a role in the pathophysiology of inflammatory bowel disease. Because inflammatory bowel disease is known to elevate the risk of colon cancer, we examined postulated roles for TRPV-1-driven neuroinflammation in promoting colitis-associated and spontaneous colon cancer development. Using a well-established model of colitis-associated cancer (CAC), we found that mice genetically deficient in TRPV-1 showed a higher incidence and number of tumors in the distal colon. In like manner, genetic deficiency of TRPV-1 in the APC(Min/+) model of spontaneous colon cancer accentuated the number of colonic adenomas formed. Mechanistic analyses in the CAC model revealed an increased infiltration of inflammatory cells into the tumors along with elevated expression of interleukin (IL)-6 and IL-11 and activation of the STAT3 and NF-κB signaling pathways. Notably, TPRV-1-deficient mice exhibited a defect in expression of the anti-inflammatory neuropeptides, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) which contributed to the generation of a local proinflammatory environment. Together, our findings argue that by limiting neuroinflammatory processes, TRPV-1 exerts a protective role that restricts the initiation and progression of colon cancer.
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba, Universidad de Córdoba, Córdoba, Spain.
authors.forename: Amaya G
authors.initials: AG
authors.lastname: Vinuesa
authors.forename: Rocío
authors.initials: R
authors.lastname: Sancho
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Limones
authors.forename: Axel
authors.initials: A
authors.lastname: Behrens
authors.forename: Peter
authors.initials: P
authors.lastname: ten Dijke
authors.forename: Marco A
authors.initials: MA
authors.lastname: Calzado
authors.forename: Eduardo
authors.initials: E
authors.lastname: Muñoz
mesh_terms: D000818:Animals; D003092:Colitis / Q000150:complications / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000209:etiology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics; D017491:Genes, APC; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016328:NF-kappa B / Q000502:physiology; D020078:Neurogenic Inflammation / Q000517:prevention & control*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000502:physiology; D050916:TRPV Cation Channels / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000235:genetics
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014660:Vasoactive Intestinal Peptide