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

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 2013
Externally publishedYes

Fingerprint

Complement Factor H
Curcumin
Glomerulonephritis
Antigen-Antibody Complex
Serum Sickness
Apoferritins
Kidney
Complement Activation
Macrophages
Albuminuria
Chemokine CCL2
Blood Urea Nitrogen
Transforming Growth Factors
Laminin
Inbred C57BL Mouse
Fibronectins
Peroxidase
Cicatrix
Proteins
B-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Jacob, A., Chaves, L., Eadon, M., Chang, A., Quigg, R. J., & Alexander, J. J. (2013). Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice. Immunology, 139(3), 328-337. https://doi.org/10.1111/imm.12079

Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice. / Jacob, Alexander; Chaves, Lee; Eadon, Michael; Chang, Anthony; Quigg, Richard J.; Alexander, Jessy J.

In: Immunology, Vol. 139, No. 3, 07.2013, p. 328-337.

Research output: Contribution to journalArticle

Jacob, A, Chaves, L, Eadon, M, Chang, A, Quigg, RJ & Alexander, JJ 2013, 'Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice', Immunology, vol. 139, no. 3, pp. 328-337. https://doi.org/10.1111/imm.12079
Jacob, Alexander ; Chaves, Lee ; Eadon, Michael ; Chang, Anthony ; Quigg, Richard J. ; Alexander, Jessy J. / Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice. In: Immunology. 2013 ; Vol. 139, No. 3. pp. 328-337.
@article{8ba31f7bff7242f0b0c4da987ae8882f,
title = "Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice",
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.",
keywords = "Complement factor H, Curcumin, Glomerulonephritis, Inflammation, Serum sickness",
author = "Alexander Jacob and Lee Chaves and Michael Eadon and Anthony Chang and Quigg, {Richard J.} and Alexander, {Jessy J.}",
year = "2013",
month = "7",
doi = "10.1111/imm.12079",
language = "English (US)",
volume = "139",
pages = "328--337",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice

AU - Jacob, Alexander

AU - Chaves, Lee

AU - Eadon, Michael

AU - Chang, Anthony

AU - Quigg, Richard J.

AU - Alexander, Jessy J.

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

KW - Complement factor H

KW - Curcumin

KW - Glomerulonephritis

KW - Inflammation

KW - Serum sickness

UR - http://www.scopus.com/inward/record.url?scp=84879235951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879235951&partnerID=8YFLogxK

U2 - 10.1111/imm.12079

DO - 10.1111/imm.12079

M3 - Article

C2 - 23347386

AN - SCOPUS:84879235951

VL - 139

SP - 328

EP - 337

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 3

ER -