TY - JOUR
T1 - Induction of the synthesis of the C-X-C chemokine interferon-γ-inducible protein-10 in experimental canine endotoxemia
AU - Frangogiannis, Nikolaos G.
AU - Mendoza, Leonardo H.
AU - Smith, C. Wayne
AU - Michael, Lloyd H.
AU - Entman, Mark L.
N1 - Funding Information:
This study was supported by NIH grant HL-42550 and the DeBakey Heart Center
PY - 2000
Y1 - 2000
N2 - 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-γ-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-α (TNF-α) and interleukin-1β (IL-1β) induced a marked upregulation of IP-10 message in canine venular endothelial cells. IP-10 expression in TNF-α-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-α, IL-1β, and M-CSF are potent inducers of IP-10 in canine endothelial cells and may indirectly mediate lymphocyte chemotaxis and activation in inflammatory processes.
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-γ-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-α (TNF-α) and interleukin-1β (IL-1β) induced a marked upregulation of IP-10 message in canine venular endothelial cells. IP-10 expression in TNF-α-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-α, IL-1β, and M-CSF are potent inducers of IP-10 in canine endothelial cells and may indirectly mediate lymphocyte chemotaxis and activation in inflammatory processes.
KW - Chemokine
KW - Cytokine
KW - Dog
KW - Endothelium
KW - Endotoxin
KW - Interleukin-1β
KW - Lymphocyte
KW - Macrophage colony-stimulating factor
KW - Tumor necrosis factor-α
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U2 - 10.1007/s004410000274
DO - 10.1007/s004410000274
M3 - Article
C2 - 11151448
AN - SCOPUS:0033672021
SN - 0302-766X
VL - 302
SP - 365
EP - 376
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 3
ER -