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

被引：4

作者：

Torigoe, Miki ^{[1
]}

Obata, Yoko ^{[1
]}

Inoue, Hiro ^{[1
]}

Torigoe, Kenta ^{[1
]}

Kinoshita, Akira ^{[2
]}

Koji, Takehiko ^{[3
]}

Mukae, Hiroshi ^{[4
]}

Nishino, Tomoya ^{[1
]}

机构：

[1] Nagasaki Univ, Dept Nephrol, Grad Sch Biomed Sci, 1-7-1 Sakamoto, Nagasaki 8528501, Japan

[2] Nagasaki Univ, Dept Human Genet, Grad Sch Biomed Sci, 1-12-4 Sakamoto, Nagasaki 8528523, Japan

[3] Nagasaki Univ, Dept Histol & Cell Biol, Grad Sch Biomed Sci, 1-12-4 Sakamoto, Nagasaki 8528523, Japan

[4] Nagasaki Univ, Dept Resp Med, Grad Sch Biomed Sci, 1-7-1 Sakamoto, Nagasaki 8528501, Japan

来源：

CLINICAL AND EXPERIMENTAL NEPHROLOGY | 2023年 / 27卷 / 02期

关键词：

Hydroxychloroquine; Anti-GBM glomerulonephritis; Crescentic glomerulonephritis; JNK; p38; MAPK; Macrophages; LOCAL MACROPHAGE PROLIFERATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ALPHA-3; CHAIN; IV COLLAGEN; GLOMERULONEPHRITIS; P38;

D O I：

10.1007/s10157-022-02285-y

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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-alpha. 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.

引用

页码：110 / 121

页数：12

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