| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Generation and Systemic Release
1 The Department of Medicine, University of Washington, Seattle, WA, USA; Fred Hutchinson Cancer Research Center, Seattle, WA, USA
* To whom correspondence should be addressed. E-mail: dzager{at}fhcrc.org.
Background: Endotoxemia (LPS) can exacerbate ischemic tubular injury and acute renal
failure (ARF). The present study tested the following hypothesis: that acute ischemic
damage sensitizes the kidney to LPS- mediated TNF-
generation, a process which can
worsen inflammation and cytotoxicity. Methods: CD-1 mice underwent 15 min of
unilateral renal ischemia. LPS (10 mg/Kg IV), or its vehicle, were injected either 45 min
prior to, or 18 hrs after, the ischemic event. TNF- responses were gauged 2 hrs post
LPS injection by measuring plasma / renal cortical TNF-, and renal cortical TNF-
mRNA. Values were contrasted to those obtained in sham operated mice, or in
contralateral, non ischemic kidneys. TNF- generation by isolated mouse proximal
tubules (PTs), and by cultured proximal tubule (HK-2) cells, in response to
hypoxia/reoxygenation (H/R), oxidant stress, antimycin A (AA), or LPS were also
assessed. Results: Ischemia/reperfusion (I/R), by itself, did not raise plasma or renal
cortical TNF- or its mRNA. However, this same ischemic insult dramatically sensitized
mice to LPS mediated- TNF- increases in both plasma and kidney (~2 fold). During late
reperfusion, increased TNF- mRNA levels also resulted. PTS generated TNF- in
response to injury. Neither AA nor LPS alone induced an HK-2 cell TNF- response.
However, when present together, AA + LPS induced ~2-5 fold increases in TNF- /
TNF- mRNA. Conclusions: Modest I/R injury, and in vitro HK-2 cell mitochondrial
inhibition (AA), can dramatically sensitize the kidney / proximal tubules, to LPS
mediated- TNF- generation, and increases in TNF- mRNA. That ischemia can 'prime'
tubules to LPS response(s), could have potentially important implications for sepsis
syndrome, concomitant renal ischemia, and for the induction of ARF.
This article has been cited by other articles:
|
|
 |
|
  R. A. Zager, A. C. M. Johnson, and A. Geballe Gentamicin suppresses endotoxin-driven TNF-{alpha} production in human and mouse proximal tubule cells Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1373 - F1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mitra, S. Bansal, W. Wang, S. Falk, E. Zolty, and R. W. Schrier Erythropoietin ameliorates renal dysfunction during endotoxaemia Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2349 - 2353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Zager "Subclinical" gentamicin nephrotoxicity: a potential risk factor for exaggerated endotoxin-driven TNF-{alpha} production Am J Physiol Renal Physiol, July 1, 2007; 293(1): F43 - F49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bolisetty and A. Agarwal Subclinical kidney injury incites endotoxin hyperresponsiveness Am J Physiol Renal Physiol, July 1, 2007; 293(1): F41 - F42. [Full Text] [PDF]
|
|
|
|
|
|
G. Ramesh, B. Zhang, S. Uematsu, S. Akira, and W. B. Reeves Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice Am J Physiol Renal Physiol, July 1, 2007; 293(1): F325 - F332. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
