Protective role of neurotrophins in experimental inflammation of the rat gut.
OBJECTIVE
Sensory neuropeptides modulate the mucosal response to inflammation in experimental colitis. Because nerve growth factor (NGF) regulates the expression of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) and is implicated as a link between the nervous system and the immune system in the inflammatory process, we investigated the functional role of NGF and neurotrophin-3 during experimental colitis.


METHODS
Immunoneutralizing antibodies specific for NGF and neurotrophin (NT)-3 were used to block their endogenous activity. Mild trinitrobenzene sulfonic acid (TNBS) colitis was induced, and damage scores were assessed after 1 week. Neuropeptide content in the colon and NT messenger RNA (mRNA) expression were determined.


RESULTS
The pretreatment with anti-NGF or anti-NT-3 caused a significant 2-3-fold increase in the severity of the experimental inflammation as assessed by a macroscopic damage score, histologic ulceration score, and myeloperoxidase activity in the tissue. CGRP, but not substance P, contents in the colon were significantly reduced by NGF immunoneutralization. NGF mRNA was slightly up-regulated after NGF immunoneutralization, but NT-3 mRNA was unchanged by NT-3 immunoneutralization. CGRP mRNA was not significantly changed after 1 week of colitis by NGF or NT-3 immunoneutralization, whereas beta-preprotachykinin mRNA was up-regulated after immunoneutralization.


CONCLUSIONS
These findings suggest a regulatory role for NGF and NT-3 in experimental inflammation of the gut. This effect may be partly caused by the reduction of mucosal CGRP content caused by the NGF blockade.
Department of Medicine I, University of Ulm, Ulm, Germany. max.reinshagen@medizin.uni-ulm.de
M
M
Reinshagen
H
H
Rohm
M
M
Steinkamp
K
K
Lieb
I
I
Geerling
A
A
Von Herbay
G
G
Flämig
V E
VE
Eysselein
G
G
Adler
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000737:chemistry / Q000276:immunology / Q000294:innervation; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics / Q000276:immunology*; D020933:Neurotrophin 3 / Q000235:genetics / Q000276:immunology*; D009500:Neutralization Tests; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000235:genetics; D020812:Receptor, trkC / Q000235:genetics; D013373:Substance P / Q000235:genetics; D015320:Tachykinins / Q000235:genetics; D014302:Trinitrobenzenesulfonic Acid
D000906:Antibodies; D020933:Neurotrophin 3; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D014302:Trinitrobenzenesulfonic Acid; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020812:Receptor, trkC; D015740:Calcitonin Gene-Related Peptide