IL-1 and TNF independent pathways mediate ICAM-1/VCAM-1 up-regulation in ischemia reperfusion injury.
In vitro studies have suggested that targeting interleukin (IL)-1 and tumor necrosis factor (TNF) can be used to regulate intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and potentially treat kidney inflammation. We therefore evaluated ICAM-1 and VCAM-1 regulation in knockout (KO) mice deficient in both IL-1 receptor 1 (R1) and TNF-R1 during renal ischemia reperfusion injury. ICAM-1 and VCAM-1 mRNA expression was measured with specific murine probes and Northern blotting (n =4/group). Protein expression was measured using immunohistochemistry. Serum creatinine (SCr), tubular histology, and neutrophil infiltration into postischemic kidneys were also quantified. ICAM-1 and VCAM-1 mRNA expression increased in both wild-type (WT) and KO mice at 2, 6, and 24 h. Protein expression of ICAM-1 and VCAM-1 was also increased at 24 h postischemia. SCr levels and tubular necrosis scores were comparable in WT and KO mice at 24 and 48 h. Neutrophil migration in KO mice was decreased at 24 h but comparable to WT at 48 h. These data demonstrate that IL-1 and TNF are not essential for postischemic increases in ICAM-1 and VCAM-1.
Burne
M J
MJ
Nephrology Division, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415, USA.
Elghandour
A
A
Haq
M
M
Saba
S R
SR
Norman
J
J
Condon
T
T
Bennett
F
F
Rabb
H
H
D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine