PMID- 11151448 OWN - NLM STAT- MEDLINE DCOM- 20010315 LR - 20190720 IS - 0302-766X (Print) IS - 0302-766X (Linking) VI - 302 IP - 3 DP - 2000 Dec TI - Induction of the synthesis of the C-X-C chemokine interferon-gamma-inducible protein-10 in experimental canine endotoxemia. PG - 365-76 AB - Endotoxemia is associated with a systemic inflammatory response leading to organ-specific leukocyte recruitment and tissue injury. Chemokine expression has been demonstrated in various models of sepsis and may mediate tissue infiltration with inflammatory cells. In this study we examined expression of the C-X-C chemokine interferon-gamma-inducible protein-10 (IP-10), a potent T-lymphocyte chemoattractant, in a canine model of endotoxemia and investigated mechanisms of cytokine-mediated IP-10 induction in endothelial cells. Control canine tissues showed negligible expression of IP-10 message, with the exception of the spleen. Endotoxemic dogs demonstrated a robust induction of IP-10 mRNA in the heart, lung, kidney, liver, and spleen. Immunohistochemical studies indicated that IP-10 was predominantly localized in cardiac venular endothelial cells, bronchial epithelial cells, renal mesangial cells, and in the splenic red pulp of endotoxemic dogs. In addition, IP-10 expression was associated with T-lymphocyte infiltration in canine tissues. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) induced a marked upregulation of IP-10 message in canine venular endothelial cells. IP-10 expression in TNF-alpha-stimulated endothelial cells peaked at 6 h of stimulation and returned to baseline levels after 24 h. In addition, macrophage colony-stimulating factor (M-CSF) induced a dose-dependent induction of IP-10 mRNA in canine endothelial cells. M-CSF-mediated IP-10 expression peaked after 6 h of incubation and returned to baseline levels after 24 h. Canine endotoxemia is associated with a robust early expression of IP-10 in multiple tissues. IP-10 induction may be important in regulating lymphocyte recruitment and function. TNF-alpha, IL-1 beta, and M-CSF are potent inducers of IP-10 in canine endothelial cells and may indirectly mediate lymphocyte chemotaxis and activation in inflammatory processes. FAU - Frangogiannis, N G AU - Frangogiannis NG AD - Section of Cardiovascular Sciences, Department of Medicine, One Baylor Plaza M/S F-602, Baylor College of Medicine, Houston, TX 77030, USA. ngf@bcm.tmc.edu FAU - Mendoza, L H AU - Mendoza LH FAU - Smith, C W AU - Smith CW FAU - Michael, L H AU - Michael LH FAU - Entman, M L AU - Entman ML LA - eng GR - HL-42550/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (Chemokine CXCL10) RN - 0 (Chemokines, CXC) RN - 0 (Endotoxins) RN - 0 (Interleukin-1) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Base Sequence MH - Cells, Cultured MH - Chemokine CXCL10 MH - Chemokines, CXC/biosynthesis/*genetics MH - Dogs MH - Endothelium/cytology/drug effects/immunology MH - Endotoxemia/*immunology MH - Endotoxins/pharmacology MH - Female MH - Humans MH - Interleukin-1/pharmacology MH - Macrophage Colony-Stimulating Factor/pharmacology MH - Male MH - Molecular Sequence Data MH - RNA, Messenger/biosynthesis MH - Sequence Homology, Nucleic Acid MH - T-Lymphocytes/immunology MH - Transcriptional Activation MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2001/01/11 11:00 MHDA- 2001/03/17 10:01 CRDT- 2001/01/11 11:00 PHST- 2001/01/11 11:00 [pubmed] PHST- 2001/03/17 10:01 [medline] PHST- 2001/01/11 11:00 [entrez] AID - 10.1007/s004410000274 [doi] PST - ppublish SO - Cell Tissue Res. 2000 Dec;302(3):365-76. doi: 10.1007/s004410000274.