Curcumin alleviates immune‐complex‐mediated glomerulonephritis in factor‐H‐deficient mice. Issue 3 (13th June 2013)

• Record Type: Journal Article
• Authors: Jacob, Alexander; Chaves, Lee; Eadon, Michael T.; Chang, Anthony; Quigg, Richard J.; Alexander, Jessy J.
• Is Part Of: Immunology. Volume 139:Issue 3(2013:Jul.)
• Page Start: 328
• Page End: 337
• Publication Date: 2013-06-13
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12079
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12079-abs-0001"> <title>Summary</title> <p>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<sup>−/−</sup>) 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, <italic>P</italic> < 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<sup>+</sup> B cells and the ratio of CD19 : CD3 cells (<italic>P</italic> < 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.</p> </abstract>