Open AccessTris DBA ameliorates IgA nephropathy by blunting the activating signal of NLRP3 inflammasome through SIRT1‐ and SIRT3‐mediated autophagy induction
Author(s) -
Wu ChungYao,
Hua KuoFeng,
Yang ShinRuen,
Tsai YiShan,
Yang ShunMin,
Hsieh ChihYu,
Wu ChiaChao,
Chang JiaFeng,
Arbiser Jack L.,
Chang ChizTzung,
Chen Ann,
Ka ShukMan
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15663
Subject(s) - inflammasome , autophagy , cancer research , medicine , inflammation , nalp3 , immunology , microbiology and biotechnology , chemistry , biology , apoptosis , biochemistry
Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small‐molecule palladium complex, can inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukaemia and multiple myeloma. Given that this compound is particularly active against B‐cell malignancies, we have been suggested that it can alleviate immune complexes (ICs)–mediated conditions, especially IgA nephropathy (IgAN). The therapeutic effects of Tris DBA on glomerular cell proliferation and renal inflammation and mechanism of action were examined in a mouse model of IgAN. Treatment of IgAN mice with Tris DBA resulted in markedly improved renal function, albuminuria and renal pathology, including glomerular cell proliferation, neutrophil infiltration, sclerosis and periglomerular inflammation in the renal interstitium, together with ( Clin J Am Soc Nephrol . 2011, 6 , 1301‐1307) reduced mitochondrial ROS generation; ( Am J Physiol‐Renal Physiol . 2011. 301 , F1218‐F1230) differentially regulated autophagy and NLRP3 inflammasome; ( Clin J Am Soc Nephrol . 2012, 7 , 427‐436) inhibited phosphorylation of JNK, ERK and p38 MAPK signalling pathways, and priming signal of the NLRP3 inflammasome; and ( Free Radic Biol Med . 2013, 61 , 285‐297) blunted NLRP3 inflammasome activation through SIRT1‐ and SIRT3‐mediated autophagy induction, in renal tissues or cultured macrophages. In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs‐mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.