Sophocarpine attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-B activation

被引:37
作者
Li, Xiuzhen [1 ]
Wang, Mengjun [1 ]
Hong, Hong [1 ]
Luo, Congjuan [2 ]
Liu, Zewei [1 ]
Yang, Ruiheng [1 ]
机构
[1] Liaocheng Peoples Hosp, Dept Nephrol, 67 West Dongchang Rd, Liaocheng 252000, Shandong, Peoples R China
[2] Qingdao Univ, Affiliated Hosp, Dept Nephrol, 16 Jiangsu Rd, Qingdao 256603, Shandong, Peoples R China
基金
美国国家科学基金会;
关键词
Sophocarpine; Lupus nephritis (LN); NLRP3; inflammasome; NF-B; KAPPA-B; PATHOGENESIS; MACROPHAGES; RECEPTORS; CELLS; MICE;
D O I
10.1007/s12026-018-9012-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Inflammation contributes to the pathogenesis of lupus nephritis (LN), which is the most serious complication that increases mortality of systemic lupus erythematosus (SLE). Sophocarpine is a type of quinolizidine alkaloid that possesses anti-inflammatory property. This study investigated the speculation that sophocarpine might play a beneficial effect in LN. Female MRL/lpr mice received sophocarpine treatment for 8weeks. Renal function and histopathology were evaluated. The level of immune complex deposition was measured by immunofluorescent staining, and the levels of proinflammatory cytokines (IL-1, IL-6, and TNF-) and anti-double-stranded DNA (anti-dsDNA) antibodies were measured by ELISA. Western blotting was carried out to evaluate the levels of proteins involved in NLRP3 inflammasome and NF-B pathway. Sophocarpine treatment reduced urine protein excretion, blood urea nitrogen, and attenuated renal tissue damage. The levels of renal immune complex deposition, serum anti-dsDNA, and serum and renal inflammatory cytokines were significantly reduced by sophocarpine. Sophocarpine treatment reduced the levels of proteins that form NLRP3 inflammasome. Activation of NF-B in the kidney was inhibited by sophocarpine. Sophocarpine could ameliorate experimental LN in MRL/lpr. These effects might be through suppressing NLRP3 inflammasome and NF-B pathway.
引用
收藏
页码:521 / 527
页数:7
相关论文
共 23 条
[1]  
Alcocer-Gomez E, 2017, ADV PROTEIN CHEM STR, P127
[2]   Cutting Edge: NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression [J].
Bauernfeind, Franz G. ;
Horvath, Gabor ;
Stutz, Andrea ;
Alnemri, Emad S. ;
MacDonald, Kelly ;
Speert, David ;
Fernandes-Alnemri, Teresa ;
Wu, Jianghong ;
Monks, Brian G. ;
Fitzgerald, Katherine A. ;
Hornung, Veit ;
Latz, Eicke .
JOURNAL OF IMMUNOLOGY, 2009, 183 (02) :787-791
[3]   The role of nuclear factor-kappa B in cytokine gene regulation [J].
Blackwell, TS ;
Christman, JW .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1997, 17 (01) :3-9
[4]   Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-κB and MAPKs signaling pathways [J].
Gao, Yonglin ;
Jiang, Wanglin ;
Dong, Chaohua ;
Li, Chunmei ;
Fu, Xuejun ;
Min, Li ;
Tian, Jingwei ;
Jin, Haizhu ;
Shen, Jingyu .
TOXICOLOGY IN VITRO, 2012, 26 (01) :1-6
[5]   Anti-nociceptive and anti-inflammatory activity of sophocarpine [J].
Gao, Yonglin ;
Li, Guisheng ;
Li, Chunmei ;
Zhu, Xiaoyin ;
Li, Min ;
Fu, Chaolin ;
Li, Bafang .
JOURNAL OF ETHNOPHARMACOLOGY, 2009, 125 (02) :324-329
[6]   The inflammasome and lupus: another innate immune mechanism contributing to disease pathogenesis? [J].
Kahlenberg, J. Michelle ;
Kaplan, Mariana J. .
CURRENT OPINION IN RHEUMATOLOGY, 2014, 26 (05) :475-481
[7]   Neutrophil Extracellular Trap-Associated Protein Activation of the NLRP3 Inflammasome Is Enhanced in Lupus Macrophages [J].
Kahlenberg, J. Michelle ;
Carmona-Rivera, Carmelo ;
Smith, Carolyne K. ;
Kaplan, Mariana J. .
JOURNAL OF IMMUNOLOGY, 2013, 190 (03) :1217-1226
[8]   Corticosteroids in Lupus Nephritis and Central Nervous System Lupus [J].
Kamen, Diane L. ;
Zollars, Eric S. .
RHEUMATIC DISEASE CLINICS OF NORTH AMERICA, 2016, 42 (01) :63-+
[9]   Signaling to NF-κB by Toll-like receptors [J].
Kawai, Taro ;
Akira, Shizuo .
TRENDS IN MOLECULAR MEDICINE, 2007, 13 (11) :460-469
[10]   Cellular interactions in the pathogenesis of lupus nephritis: The role of T cells and macrophages in the amplification of the inflammatory process in the kidney [J].
Kuroiwa, T ;
Lee, EG .
LUPUS, 1998, 7 (09) :597-603