Hydroxychloroquine suppresses anti-GBM nephritis via inhibition of JNK/p38 MAPK signaling.

Abstract

BACKGROUND:

Anti-glomerular basement membrane (anti-GBM) nephritis, characterized by glomerular crescent formation, requires early treatment because of poor prognosis. Hydroxychloroquine (HCQ) is an antimalarial drug with known immunomodulatory, anti-inflammatory, and autophagy inhibitory effects; it is recognized in the treatment of autoimmune diseases such as systemic lupus erythematosus. However, its effect on anti-GBM nephritis remains unknown. In this study, we investigated the effect of HCQ on anti-GBM nephritis in rats.

METHODS:

Seven-weeks-old male WKY rats were administered anti-GBM serum to induce anti-GBM nephritis. Either HCQ or vehicle control was administered from day 0 to day 7 after the induction of nephritis. Renal function was assessed by measuring serum creatinine, proteinuria, and hematuria. Renal histological changes were assessed by PAS staining and Masson trichrome staining, and infiltration of macrophages was assessed by ED-1 staining. Mitogen-activated protein kinase (MAPK) was evaluated by western blotting, while chemokine and inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay using urine sample.

RESULTS:

HCQ treatment suppressed the decline in renal function. Histologically, extracapillary and intracapillary proliferations were observed from day 1, while fibrinoid necrosis and ED-1 positive cells were observed from day 3. Rats with anti-GBM nephritis showed high levels of monocyte chemotactic protein-1 and tumor necrosis factor-α. These changes were significantly suppressed following HCQ treatment. In addition, HCQ suppressed JNK/p38 MAPK phosphorylation.

CONCLUSION:

HCQ attenuates anti-GBM nephritis by exerting its anti-inflammatory effects via the inhibition of JNK/p38 MAPK activation, indicating its therapeutic potential against anti-GBM nephritis.

• Authors: Miki Torigoe, Yoko Obata, Hiro Inoue, Kenta Torigoe, Akira Kinoshita, Takehiko Koji, Hiroshi Mukae, Tomoya Nishino
• Journal: Clinical and experimental nephrology (Clin Exp Nephrol) Vol. 27 Issue 2 Pg. 110-121 (Feb 2023) ISSN: 1437-7799 [Electronic] Japan
• PMID: 36264415 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to The Japanese Society of Nephrology.

Chemical References

• antiglomerular basement membrane antibody
• p38 Mitogen-Activated Protein Kinases
• Hydroxychloroquine
• Anti-Inflammatory Agents

Topics

• Rats
• Male
• Animals
• p38 Mitogen-Activated Protein Kinases
• Hydroxychloroquine (pharmacology, therapeutic use)
• Rats, Inbred WKY
• Nephritis (drug therapy)
• Anti-Inflammatory Agents (therapeutic use)
• Glomerulonephritis (pathology)