Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice

Alexander Jacob, Lee Chaves, Michael T. Eadon, Anthony Chang, Richard J. Quigg, Jessy J. Alexander

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Summary: 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.

Original languageEnglish (US)
Pages (from-to)328-337
Number of pages10
JournalImmunology
Volume139
Issue number3
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Keywords

  • Complement factor H
  • Curcumin
  • Glomerulonephritis
  • Inflammation
  • Serum sickness

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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