{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T07:20:07Z","timestamp":1788592807484,"version":"build-2803163510"},"reference-count":36,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>TNF-\u03b1 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)-1\u03b1] and C-X-C chemokines [MIP-2 and cytokine-induced neutrophil chemoattractant (CINC)-2\u03b1] mediate chemotaxis of monocytes and neutrophils, respectively. We examined the roles of TNF-\u03b1 and dynamics of chemokine expression in gastric ulceration including ulcer recurrence and indomethacin-induced injury. Rats with healed chronic gastric ulcers received intraperitoneal TNF-\u03b1 to induce ulcer recurrence. Some rats were given neutralizing antibodies against neutrophils or MCP-1 together with TNF-\u03b1. In a separate experiment, rats were orally administered 20 mg\/kg indomethacin with or without pretreatment with pentoxifylline (an inhibitor of TNF-\u03b1 synthesis) or anti-MCP-1 antibody. TNF-\u03b1 (1 \u03bcg\/kg) induced gastric ulcer recurrence after 48 h, which was completely prevented by anti-neutrophil antibody. TNF-\u03b1 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-2\u03b1 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-\u03b1\/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-2\u03b1). Anti-MCP-1 antibody also inhibited the injury and these inflammatory responses but did not affect TNF-\u03b1 mRNA expression. In conclusion, increased MCP-1 triggered by TNF-\u03b1 may play a key role in gastric ulceration by regulating leukocyte recruitment and chemokine expression.<\/jats:p>","DOI":"10.1152\/ajpgi.00372.2003","type":"journal-article","created":{"date-parts":[[2004,6,18]],"date-time":"2004-06-18T00:29:52Z","timestamp":1087518592000},"page":"G919-G928","source":"Crossref","is-referenced-by-count":47,"title":["Monocyte chemotactic protein-1 regulates leukocyte recruitment during gastric ulcer recurrence induced by tumor necrosis 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