| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
* To whom correspondence should be addressed. E-mail: watanabet{at}med.osaka-cu.ac.jp.
TNF-
has numerous biological activities including induction of chemokine expression, and is
involved in many gastric injuries. C-C chemokines (MCP-1 and MIP-1) and C-X-C chemokines
(MIP-2 and CINC-2) mediate chemotaxis of monocytes and neutrophils, respectively. We
examined the roles of TNF- and dynamics of chemokine expression in gastric ulceration including
ulcer recurrence and indomethacin-induced injury. Rats with healed chronic gastric ulcers received
intraperitoneal TNF- to induce ulcer recurrence. Some rats were given neutralizing antibodies
against neutrophils or MCP-1 together with TNF-. In a separate experiment, rats were orally
administered 20 mg/kg indomethacin with or without pretreatment with pentoxifylline (an inhibitor
of TNF- synthesis) or anti-MCP-1 antibody. TNF- (1 µg/kg) induced gastric ulcer recurrence
after 48 hours, which was completely prevented by anti-neutrophil antibody. TNF- increased the
number of macrophages and MCP-1 mRNA expression in scarred mucosa from 4 hours, whereas it
increased myeloperoxidase activities (marker of neutrophil infiltration) and mRNA expression of
MIP-2 and CINC-2 from 24 hours. Anti-MCP-1 antibody inhibited leukocyte infiltration with
reduction of the levels of C-X-C chemokines, and prevented ulcer recurrence. Indomethacin
treatment increased TNF-/chemokines mRNA expression from 30 minutes, and induced
macroscopic erosions after 4 hours. Pentoxifylline inhibited the indomethacin-induced gastric injury
with reduction of neutrophil infiltration and expression of chemokine (MCP-1, MIP-2 and CINC-2).
Anti-MCP-1 antibody also inhibited the injury and these inflammatory responses, but did not affect TNF- mRNA expression. In conclusion, increased MCP-1 triggered by TNF- may play a key role
in gastric ulceration, by regulating leukocyte recruitment and chemokine expression.
This article has been cited by other articles:
|
|
 |
|
  T. Watanabe, H. Nishio, T. Tanigawa, H. Yamagami, H. Okazaki, K. Watanabe, K. Tominaga, Y. Fujiwara, N. Oshitani, T. Asahara, et al. Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid Am J Physiol Gastrointest Liver Physiol, September 1, 2009; 297(3): G506 - G513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Watanabe, K Higuchi, A Kobata, H Nishio, T Tanigawa, M Shiba, K Tominaga, Y Fujiwara, N Oshitani, T Asahara, et al. Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent Gut, February 1, 2008; 57(2): 181 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-K. Sun, T. Reding, M. Bain, M. Heikenwalder, D. Bimmler, and R. Graf Prostaglandin E2 modulates TNF-{alpha}-induced MCP-1 synthesis in pancreatic acinar cells in a PKA-dependent manner Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1196 - G1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Reding, D Bimmler, A Perren, L-K Sun, F Fortunato, F Storni, and R Graf A selective COX-2 inhibitor suppresses chronic pancreatitis in an animal model (WBN/Kob rats): significant reduction of macrophage infiltration and fibrosis Gut, August 1, 2006; 55(8): 1165 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Lokuta and A. Huttenlocher TNF-{alpha} promotes a stop signal that inhibits neutrophil polarization and migration via a p38 MAPK pathway J. Leukoc. Biol., July 1, 2005; 78(1): 210 - 219. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
