Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice.
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.
Department of Medicine, The University of Chicago, Chicago, IL, USA.
Alexander
A
Jacob
Lee
L
Chaves
Michael T
MT
Eadon
Anthony
A
Chang
Richard J
RJ
Quigg
Jessy J
JJ
Alexander
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001052:Apoferritins / Q000008:administration & dosage; D002908:Chronic Disease; D003167:Complement Activation / Q000187:drug effects; D017242:Complement Factor H / Q000172:deficiency; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007105:Immune Complex Diseases / Q000188:drug therapy*; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012713:Serum Sickness / Q000188:drug therapy*; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017242:Complement Factor H; D001052:Apoferritins; D003474:Curcumin