Early renal ischemia, with or without reperfusion, activates NFκB and increases TNF-α bioactivity in the kidney

被引:123
作者
Donnahoo, KK
Meldrum, DR
Shenkar, R
Chung, CS
Abraham, E
Harken, AH
机构
[1] Indiana Univ, Med Ctr, Dept Urol, Indianapolis, IN 46202 USA
[2] Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA
[4] Brown Univ, Sch Med, Dept Physiol, Providence, RI 02912 USA
[5] Brown Univ, Sch Med, Dept Immunol Microbiol, Providence, RI 02912 USA
关键词
transcription factors; cytotoxicity; cytokines; injury;
D O I
10.1016/S0022-5347(05)67772-5
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Acute tubular necrosis (ATN) and the ensuing renal failure induced by ischemia and reperfusion injury (I/R) remain a major cause of morbidity and mortality among patients in the intensive care unit. Although it is well established that exogenous tumor necrosis factor-alpha (TNF) induces renal injury, it remains unknown whether ischemia and/or reperfusion activates the signaling mechanisms required for renal TNF production. We hypothesized that ischemia and/or reperfusion would activate the oxidant. sensitive TNF transcription factor, nuclear factor kappa B (NF kappa B), and thereby lead to renal TNF production. Materials and Methods: Male Sprague-Dawley rats were anesthetized with sodium pentobarbital, after which various periods of renal ischemia, with or without reperfusion, were induced in fats. At different time intervals, kidneys were harvested and NF kappa B activation (electrophoretic mobility shift assay), TNF mRNA content (RT-PCR), and TNF bioactivity (WEHI-164 cell clone cytotoxicity assay) were determined. Results: Results indicate that 15 minutes of ischemia alone activates NF kappa B, whereas peak activation occurred at 30 minutes of ischemia alone. NF kappa B remained activated through 60 minutes reperfusion. Thirty minutes of ischemia is required to induce renal TNF mRNA production; however, renal TNF protein expression and bioactivity peaked following 1 hour of ischemia and 2 hours reperfusion. Conclusions: These results are the initial demonstration that renal ischemia, with or without reperfusion, activates the TNF transcription factor NF kappa B and increases TNF bioactivity in the kidney.
引用
收藏
页码:1328 / 1332
页数:5
相关论文
共 53 条
[1]   EFFICACY AND SAFETY OF MONOCLONAL-ANTIBODY TO HUMAN TUMOR-NECROSIS-FACTOR-ALPHA IN PATIENTS WITH SEPSIS SYNDROME - A RANDOMIZED, CONTROLLED, DOUBLE-BLIND, MULTICENTER CLINICAL-TRIAL [J].
ABRAHAM, E ;
WUNDERINK, R ;
SILVERMAN, H ;
PERL, TM ;
NASRAWAY, S ;
LEVY, H ;
BONE, R ;
WENZEL, RP ;
BALK, R ;
ALLRED, R ;
PENNINGTON, JE ;
WHERRY, JC .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 273 (12) :934-941
[2]   SEPSIS THERAPY TRIALS - CONTINUED DISAPPOINTMENT OR REASON FOR HOPE [J].
ABRAHAM, E ;
RAFFIN, TA .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1994, 271 (23) :1876-1878
[3]   p55 tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock - A randomized controlled multicenter trial [J].
Abraham, E ;
Glauser, MP ;
Butler, T ;
Garbino, J ;
Gelmont, D ;
Laterre, PF ;
Kudsk, K ;
Bruining, HA ;
Otto, C ;
Tobin, E ;
Zwingelstein, C ;
Lesslauer, W ;
Leighton, A .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 277 (19) :1531-1538
[4]  
AYALA A, 1990, Cytokine, V2, P170, DOI 10.1016/1043-4666(90)90012-I
[5]   NF-kappa B: Ten years after [J].
Baeuerle, PA ;
Baltimore, D .
CELL, 1996, 87 (01) :13-20
[6]  
BERTANI T, 1989, AM J PATHOL, V134, P419
[7]   PASSIVE-IMMUNIZATION AGAINST CACHECTIN TUMOR NECROSIS FACTOR PROTECTS MICE FROM LETHAL EFFECT OF ENDOTOXIN [J].
BEUTLER, B ;
MILSARK, IW ;
CERAMI, AC .
SCIENCE, 1985, 229 (4716) :869-871
[8]  
CAIN BS, 1998, IN PRESS J MOL CELL
[9]   Fibronectin augments monocyte adhesion to low-density lipoprotein-stimulated mesangial cells [J].
Chana, RS ;
Wheeler, DC .
KIDNEY INTERNATIONAL, 1999, 55 (01) :179-188
[10]   CD28-B7 blockade in organ dysfunction secondary to cold ischemia/reperfusion injury - Rapid Communication [J].
Chandraker, A ;
Takada, M ;
Nadeau, KC ;
Peach, R ;
Tilney, NL ;
Sayegh, MH .
KIDNEY INTERNATIONAL, 1997, 52 (06) :1678-1684