Document Detail

Oxidized low-density lipoprotein antigen transport induces autoimmunity in the renal tubulointerstitium.
MedLine Citation:
PMID:  22653259     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Chronic kidney disease involves inflammation/oxidative stress, which contributes to progressive kidney injury.
METHODS: Male Sprague-Dawley rats underwent 5/6 nephrectomy (Nx) or sham Nx and were sacrificed after 2 days, 2 weeks and 4 weeks. Microarray analysis expression sets over time suggested the evolution of renal lymphocyte infiltration and antigen-presenting cell (APC) activation after 5/6Nx. RT-PCR analysis also confirmed the migration and activation of lymphocytes and APCs through the upregulation of CD3, CXCR3/CXCL10 and CCR7/CCL19 mRNA in remnant kidney (RK). Purified T lymphocytes from spleen and unilateral ureteral obstruction (UUO) kidney were incubated with oxidized low-density lipoprotein (Ox-LDL)-treated major histocompatibility complex class II (MHC II)-expressing APCs. Culture supernatant was collected for mouse IFN-γ ELISA and cell proliferation was measured.
RESULTS: Ox-LDL deposited predominantly in renal tubulointerstitial areas of RK, increased over time, and co-stained with lectin-like Ox-LDL receptor in affected renal tubular cells. Both Ox-LDL and renal-specific glycoprotein Tamm-Horsfall protein were identified in renal lymph nodes. Cells co-staining for major MHC II and Ox-LDL were observed in RK and draining renal lymph nodes after 5/6Nx. Similarly, Ox-LDL was also present in tubules after UUO, CD3-positive T cells were present in the interstitium, and Ox-LDL-treated MHC II-expressing APCs induced proliferation and IFN-γ production in renal tubulointerstitial T lymphocytes isolated from kidneys after UUO.
CONCLUSIONS: These data demonstrate that the tubulointerstitial inflammatory infiltrate that accompanies chronic kidney disease reflects, at least in part, the development of autoimmunity to novel antigens generated during renal injury.
Bancha Satirapoj; Kevin W Bruhn; Cynthia C Nast; Ying Wang; Tiane Dai; Janine Lapage; Xiwei Wu; Rama Natarajan; Sharon G Adler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-25
Journal Detail:
Title:  American journal of nephrology     Volume:  35     ISSN:  1421-9670     ISO Abbreviation:  Am. J. Nephrol.     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-28     Completed Date:  2012-11-09     Revised Date:  2012-12-10    
Medline Journal Info:
Nlm Unique ID:  8109361     Medline TA:  Am J Nephrol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  520-30     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Harbor-UCLA Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA.
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MeSH Terms
Antigens, CD3 / metabolism
Cell Movement
Cell Proliferation / drug effects
Cells, Cultured
Chemokine CCL19 / metabolism
Chemokine CXCL10 / metabolism
Chronic Disease
Histocompatibility Antigens Class II / metabolism
Interferon-gamma / drug effects,  metabolism
Kidney Diseases / immunology*,  metabolism,  pathology
Kidney Tubules / immunology,  metabolism,  pathology
Lipoproteins, LDL / immunology*,  pharmacology
Lymph Nodes / metabolism
Microarray Analysis
Nephritis, Interstitial / immunology,  metabolism,  pathology
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Receptors, CCR7 / metabolism
Receptors, CXCR3 / metabolism
Scavenger Receptors, Class E / metabolism
T-Lymphocytes / metabolism*,  physiology
Ureteral Obstruction / immunology
Uromodulin / metabolism
Grant Support
Reg. No./Substance:
0/Antigens, CD3; 0/CCL19 protein, human; 0/CCR7 protein, human; 0/CXCR3 protein, human; 0/Chemokine CCL19; 0/Chemokine CXCL10; 0/Histocompatibility Antigens Class II; 0/Lipoproteins, LDL; 0/Oldlr1 protein, rat; 0/RNA, Messenger; 0/Receptors, CCR7; 0/Receptors, CXCR3; 0/Scavenger Receptors, Class E; 0/Umod protein, rat; 0/Uromodulin; 0/oxidized low density lipoprotein; 82115-62-6/Interferon-gamma

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