Capsaicin-sensitive nerve fibres induce epithelial cell proliferation, inflammatory cell immigration and transforming growth factor-alpha expression in the rat colonic mucosa in vivo.
BACKGROUND
Capsaicin-sensitive nerve fibres protect gastrointestinal mucosa in animal models of mucosal injury by modulation of mucosal blood flow and mucus secretion. The aim of our study was to evaluate the effects of capsaicin-sensitive nerve fibres in rat colonic mucosa on epithelial cell proliferation and transforming growth factor-alpha (TGFalpha) expression, which is important in mucosal defence, protection and repair.


METHODS
Male Wistar rats received either a capsaicin enema with or without giving antagonists to calcitonin-gene-related-peptide (CGRP) or substance P (SP) i.v. immediately prior to the capsaicin enemas; a capsaicin enema after sensory desensitization as described previously; or a vehicle enema. In all experiments, animals received 50 mg/kg BrdU i.v. and were killed at 2, 4, 8, 12, 24 and 48 h after the various treatments. Colonic mucosal specimens were evaluated microscopically for mucosal damage, changes in the numbers of inflammatory cells and BrdU-immunoreactive epithelial cell nuclei. In the same specimens, TGFalpha-mRNA and -protein expression were evaluated by RT-PCR and Western blot analysis using standardized procedures.


RESULTS
A significant increase in the number of mucosal inflammatory cells and an increase in BrdU-immunoreactive nuclei were detected following mucosal exposure to capsaicin. A 2-fold increase of TGFalpha mRNA and a 10-fold increase of TGFalpha protein expression were obtained 2-12 h after capsaicin enemas. The effects on the invading number of inflammatory cells and on the increase in BrdU immunoreactive epithelial cell nuclei were significantly reduced by both CGRP and SP antagonists and were abolished in rats previously sensory-desensitized.


CONCLUSIONS
Capsaicin-sensitive nerve fibres modulate epithelial cell proliferation and TGFalpha expression in colonic mucosa as well as a migration of inflammatory cells into the colonic mucosa. These effects are mediated by the neurotransmitters CGRP and SP.
Hoffmann
P
P
Dept. of Medicine 1, University of Bochum, St. Josef Hospital, Germany. peter.hoffmann@ruhr-uni-bochum.de
Mazurkiewicz
J
J
Holtmann
G
G
Gerken
G
G
Eysselein
V E
VE
Goebell
H
H
D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D002455:Cell Division / Q000502:physiology*; D003106:Colon / Q000166:cytology / Q000294:innervation* / Q000378:metabolism; D003714:Denervation; D020397:Goblet Cells / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D013373:Substance P; D009195:Peroxidase; D001973:Bromodeoxyuridine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin