| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037;
Department of Medicine, Division of Nephrology, Scripps Clinic and Green Hospital, La Jolla, CA 92037;
Department of Pathology, Scripps Clinic and Green Hospital, La Jolla, CA 92037; and
Core Microscopy Department, The Scripps Research Institute, La Jolla, CA 92037
TLRs are an evolutionarily conserved family of cell membrane proteins believed to play a significant role in innate immunity and the response to tissue injury, including that induced by ischemia. TLR signaling pathways activate transcription factors that regulate expression of prosurvival proteins, as well as proinflammatory cytokines and chemokines through one of two proximal adapter proteins, MyD88 or Toll/IL-1R domain-containing adaptor-inducing IFN-
(Trif). Our study defines the constitutive protein expression of TLR2 in kidneys of humans and mice, and provides insight into the signaling mechanisms by which a deficiency of TLR2 protects from ischemic organ injury. Our study compared and contrasted the effects of renal ischemia in wild-type mice and mice deficient in TLR2, MyD88, Trif, and MyD88 x Trif. TLR2 protein was evident in many cell types in the kidney, including renal tubules of the outer stripe of the medulla, glomeruli, and in the renal vasculature. The pattern of protein expression was similar in humans and mice. The absence of TLR2, MyD88, and MyD88 x Trif conferred both physiologic and histologic protection against sublethal ischemia at 24 h. Interestingly, TLR2-deficient mice were better protected from ischemic renal injury than those deficient for the adapter protein MyD88, raising the intriguing possibility that TLR-2-dependent/MyD88-independent pathways also contribute to kidney injury. We conclude that TLR2 protein is constitutively expressed in the kidney and plays an important role in the pathogenesis of acute ischemic injury by signaling both MyD88-dependent and MyD88-independent pathways.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Renal Research Collaborative (Scripps Green Hospital and Scripps Clinic) and by a National Institutes of Health Grant (1R01DK60151; to D.B.M.).
2 A.A.S. and T.D.H. contributed equally to this manuscript.
3 Address correspondence and reprint requests to Dr. Dianne B. McKay, Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92067. E-mail address: dmckay{at}scripps.edu
4 Abbreviations used in this paper: Trif, Toll/IL-1R domain-containing adaptor-inducing IFN-; DAMP, damage-associated molecular pattern; DAPI, 4',6-diamidino-2-phenylindole; IR, ischemia reperfusion; KC, keratinocyte-derived cytokine; WT, wild type.
This article has been cited by other articles:
|
|
 |
|
  A. E. Mullick, K. Soldau, W. B. Kiosses, T. A. Bell III, P. S. Tobias, and L. K. Curtiss Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events J. Exp. Med., February 18, 2008; 205(2): 373 - 383. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
