Faculty Opinions recommendation of Spleen tyrosine kinase is important in the production of proinflammatory cytokines and cell proliferation in human mesangial cells following stimulation with IgA1 isolated from IgA nephropathy patients.

Author(s):  
Kar Neng Lai
2021 ◽  
Vol 12 ◽  
Author(s):  
Wai Han Yiu ◽  
Kam Wa Chan ◽  
Loretta Y. Y. Chan ◽  
Joseph C. K. Leung ◽  
Kar Neng Lai ◽  
...  

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase involved in signal transduction in a variety of immune responses. It has been demonstrated that Syk plays a pathogenic role in orchestrating inflammatory responses and cell proliferation in human mesangial cells (HMC) in IgA nephropathy (IgAN). However, whether Syk is involved in tubular damage in IgAN remains unknown. Using human kidney biopsy specimens, we found that Syk was activated in renal tubules of biopsy-proven IgAN patients with an increase in total and phosphorylated levels compared to that from healthy control subjects. In vitro, cultured proximal tubular epithelial cells (PTECs) were stimulated with conditioned medium prepared from human mesangial cells incubated with polymeric IgA (IgA-HMC) from patients with IgAN or healthy control. Induction of IL-6, IL-8, and ICAM-1 synthesis from cultured PTECs incubated with IgA-HMC conditioned medium was significantly suppressed by treatment with the Syk inhibitor R406 compared to that from healthy control. Furthermore, R406 downregulated expression of phosphorylated p65 NF-κB and p-42/p-44 MAPK, and attenuated TNF-α-induced cytokine production in PTECs. Taken together, our findings suggest that Syk mediates IgA-HMC conditioned medium-induced inflammation in tubular cells via activation of NF-κB and p-42/p-44 MAPK signaling. Inhibition of Syk may be a potential therapeutic approach for tubulointerstitial injury in IgAN.


2011 ◽  
Vol 26 (11) ◽  
pp. 3451-3457 ◽  
Author(s):  
Jan Novak ◽  
Leona Raskova Kafkova ◽  
Hitoshi Suzuki ◽  
Milan Tomana ◽  
Karel Matousovic ◽  
...  

2004 ◽  
Vol 229 (10) ◽  
pp. 1053-1060 ◽  
Author(s):  
Mayumi Negishi ◽  
Hiroyuki Shimizu ◽  
Shuichi Okada ◽  
Atsushi Kuwabara ◽  
Fumikazu Okajima ◽  
...  

1999 ◽  
Vol 45 (1-3) ◽  
pp. 57-62 ◽  
Author(s):  
Celine Alric ◽  
Christiane Pecher ◽  
Jean-Loup Bascands ◽  
Jean-Pierre Girolami

Life Sciences ◽  
2009 ◽  
Vol 84 (21-22) ◽  
pp. 725-731 ◽  
Author(s):  
Tatsuya Shibata ◽  
Masahito Tamura ◽  
Narutoshi Kabashima ◽  
Ryota Serino ◽  
Masaki Tokunaga ◽  
...  

1996 ◽  
Vol 49 (3) ◽  
pp. 839-845 ◽  
Author(s):  
Kar Neng Lai ◽  
Wah Yuen To ◽  
Philip K.T. Li ◽  
Joseph C.K. Leung

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