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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-13
pubmed:abstractText
TNF-alpha has numerous biological activities, including the induction of chemokine expression, and is involved in many gastric injuries. C-C chemokines [monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha] and C-X-C chemokines [MIP-2 and cytokine-induced neutrophil chemoattractant (CINC)-2alpha] mediate chemotaxis of monocytes and neutrophils, respectively. We examined the roles of TNF-alpha and dynamics of chemokine expression in gastric ulceration including ulcer recurrence and indomethacin-induced injury. Rats with healed chronic gastric ulcers received intraperitoneal TNF-alpha to induce ulcer recurrence. Some rats were given neutralizing antibodies against neutrophils or MCP-1 together with TNF-alpha. In a separate experiment, rats were orally administered 20 mg/kg indomethacin with or without pretreatment with pentoxifylline (an inhibitor of TNF-alpha synthesis) or anti-MCP-1 antibody. TNF-alpha (1 microg/kg) induced gastric ulcer recurrence after 48 h, which was completely prevented by anti-neutrophil antibody. TNF-alpha increased the number of macrophages and MCP-1 mRNA expression in scarred mucosa from 4 h, whereas it increased MPO activities (marker of neutrophil infiltration) and mRNA expression of MIP-2 and CINC-2alpha from 24 h. 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-alpha/chemokine mRNA expression from 30 min and induced macroscopic erosions after 4 h. Pentoxifylline inhibited the indomethacin-induced gastric injury with reduction of neutrophil infiltration and expression of chemokine (MCP-1, MIP-2, and CINC-2alpha). Anti-MCP-1 antibody also inhibited the injury and these inflammatory responses but did not affect TNF-alpha mRNA expression. In conclusion, increased MCP-1 triggered by TNF-alpha may play a key role in gastric ulceration by regulating leukocyte recruitment and chemokine expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-Pyridinylmethylsulfinylbenzimidazo..., http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Anti-Ulcer Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Benzimidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL3, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL4, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL2, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Cxcl2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Omeprazole, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/rabeprazole
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
287
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G919-28
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15205118-2-Pyridinylmethylsulfinylbenzimidazoles, pubmed-meshheading:15205118-Animals, pubmed-meshheading:15205118-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:15205118-Anti-Ulcer Agents, pubmed-meshheading:15205118-Antibodies, pubmed-meshheading:15205118-Antineoplastic Agents, pubmed-meshheading:15205118-Benzimidazoles, pubmed-meshheading:15205118-Cell Movement, pubmed-meshheading:15205118-Chemokine CCL2, pubmed-meshheading:15205118-Chemokine CCL3, pubmed-meshheading:15205118-Chemokine CCL4, pubmed-meshheading:15205118-Chemokine CXCL2, pubmed-meshheading:15205118-Chemokines, pubmed-meshheading:15205118-Chemokines, CXC, pubmed-meshheading:15205118-Gastric Acid, pubmed-meshheading:15205118-Gastric Mucosa, pubmed-meshheading:15205118-Indomethacin, pubmed-meshheading:15205118-Intercellular Adhesion Molecule-1, pubmed-meshheading:15205118-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:15205118-Leukocytes, pubmed-meshheading:15205118-Macrophage Inflammatory Proteins, pubmed-meshheading:15205118-Male, pubmed-meshheading:15205118-Omeprazole, pubmed-meshheading:15205118-RNA, Messenger, pubmed-meshheading:15205118-Rats, pubmed-meshheading:15205118-Rats, Wistar, pubmed-meshheading:15205118-Recurrence, pubmed-meshheading:15205118-Specific Pathogen-Free Organisms, pubmed-meshheading:15205118-Stomach Ulcer, pubmed-meshheading:15205118-Tumor Necrosis Factor-alpha
pubmed:year
2004
pubmed:articleTitle
Monocyte chemotactic protein-1 regulates leukocyte recruitment during gastric ulcer recurrence induced by tumor necrosis factor-alpha.
pubmed:affiliation
Dept. of Gastroenterology, Osaka City Univ. Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. watanabet@med.osaka-cu.ac.jp
pubmed:publicationType
Journal Article