Heat shock protein 60 is released in immune-mediated glomerulonephritis and aggravates disease: In vivo evidence for an immunologic danger signal

Lang, Andreas, Benke, Dirk, Eitner, Frank, Engel, Daniel, Ehrlich, Svenja, Breloer, Minka, Hamilton-Williams, Emma, Specht, Sabine, Hoerauf, Achim, Floege, Jürgen, von Bonin, Arne and Kurts, Christian (2005) Heat shock protein 60 is released in immune-mediated glomerulonephritis and aggravates disease: In vivo evidence for an immunologic danger signal. Journal of the American Society of Nephrology, 16 2: 383-391. doi:10.1681/ASN.2004040276


Author Lang, Andreas
Benke, Dirk
Eitner, Frank
Engel, Daniel
Ehrlich, Svenja
Breloer, Minka
Hamilton-Williams, Emma
Specht, Sabine
Hoerauf, Achim
Floege, Jürgen
von Bonin, Arne
Kurts, Christian
Title Heat shock protein 60 is released in immune-mediated glomerulonephritis and aggravates disease: In vivo evidence for an immunologic danger signal
Journal name Journal of the American Society of Nephrology   Check publisher's open access policy
ISSN 1046-6673
1533-3450
Publication date 2005-02
Sub-type Article (original research)
DOI 10.1681/ASN.2004040276
Volume 16
Issue 2
Start page 383
End page 391
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society of Nephrology
Language eng
Abstract Heat shock proteins (Hsp) are ubiquitous intracellular proteins that can be released in various forms of cellular stress. Some Hsp, such as Hsp60, have been shown to stimulate directly T cell-mediated immune responses in vitro. Here, it is demonstrated that Hsp60 is released from the kidneys and excreted into the urine of mice with nephrotoxic nephritis (NTN), a model of rapidly progressive glomerulonephritis. For examining the functional relevance of Hsp60 release, this protein was injected into mice with subnephritogenic NTN, in which only transient proteinuria and minimal organ damage occur that do not progress to terminal kidney failure. Injection of Hsp60 strikingly aggravated disease, as evidenced by global glomerular necrosis, tubulointerstitial damage, and complete anuria after 10 to 12 d. This effect was mediated neither by endotoxin contaminations of Hsp60 nor by autologous antibodies. It was strictly T cell dependent but not associated with a systemic Th1/Th2 shift. Thus, Hsp60 is an endogenous mediator stimulating immune effector mechanisms that contribute to the progression of NTN. These findings demonstrate in vivo that Hsp60 fulfills criteria of immunologic danger signals and suggest that such signals may be involved in immune-mediated kidney disease.
Keyword Heat-Shock-Protein
Basement-Membrane Glomerulonephritis
Intrinsic Renal-Cells
Necrosis-Factor-Alpha
Ifn-Gamma Production
T-Cells
Dendritic Cells
Crescentic Glomerulonephritis
Interstitial Nephritis
Expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
UQ Diamantina Institute Publications
 
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