Document Detail


Oxidized low-density lipoprotein antigen transport induces autoimmunity in the renal tubulointerstitium.
MedLine Citation:
PMID:  22653259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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.
Affiliation:
Harbor-UCLA Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD3 / metabolism
Autoimmunity*
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
Male
Microarray Analysis
Nephrectomy
Nephritis, Interstitial / immunology,  metabolism,  pathology
RNA, Messenger / metabolism
Rats
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
ID/Acronym/Agency:
UL1 TR000124/TR/NCATS NIH HHS
Chemical
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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