Document Detail


Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice.
MedLine Citation:
PMID:  23347386     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh(-/-)) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19(+) B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-β and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness.
Authors:
Alexander Jacob; Lee Chaves; Michael T Eadon; Anthony Chang; Richard J Quigg; Jessy J Alexander
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-14     Completed Date:  2013-08-19     Revised Date:  2014-04-18    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  328-37     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage,  pharmacology,  therapeutic use*
Apoferritins / administration & dosage
Chronic Disease
Complement Activation / drug effects
Complement Factor H / deficiency
Curcumin / administration & dosage,  pharmacology,  therapeutic use*
Glomerulonephritis / drug therapy*,  etiology
Humans
Immune Complex Diseases / drug therapy*
Kidney Function Tests
Male
Mice
Mice, Inbred C57BL
Serum Sickness / drug therapy*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
DK041873/DK/NIDDK NIH HHS; DK055357/DK/NIDDK NIH HHS; T32 GM007019/GM/NIGMS NIH HHS; T32GM007019/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 80295-65-4/Complement Factor H; 9013-31-4/Apoferritins; IT942ZTH98/Curcumin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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