Sinomenine potentiates degranulation of RBL-2H3 basophils via up-regulation of phospholipase A2 phosphorylation by Annexin A1 cleavage and ERK phosphorylation without influencing on calcium mobilization.
Sinomenine (SIN), an alkaloid derived from the Chinese medicinal plant Sinomenium acutum, is the major component of Zhengqing Fongtong Ning (ZQFTN), a pharmaceutical drug produced by Hunan Zhengqing Pharmaceutical Co. Ltd. in China for the treatment of rheumatoid arthritis and other autoimmune diseases. Some clinic reports indicate that ZQFTN may induce an anaphylactic reaction via potentiating the degranulation of immune cells. In the current study, we aimed to examine whether SIN is capable of inducing the degranulation of basophilic leukemia 2H3 (RBL-2H3) cells to elucidate how the anaphylactic reaction occurs. The results revealed that SIN could up-regulate β-hexosaminidase levels in RBL-2H3 cells without significant cytotoxicity, suggesting that SIN could induce the degranulation of RBL-2H3 cells. Furthermore, SIN increased the release of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) in RBL-2H3 cells via promoting the expression of phosphorylated-extracellular signal-regulated kinase (P-ERK), the cleavage of Annexin A1 (ANXA1), and phosphorylated-cytosolic phospholipase A2 (P-cPLA2), as well as cyclooxygenase-2 (COX-2). The ERK inhibitor, PD98059, significantly attenuated the up-regulatory effect of SIN on cPLA2 phosphorylation. Interestingly, SIN did not significantly increase Ca(2+) influx in the cells. These findings not only explored the anaphylactic reaction and underlying mechanism of ZQFTN in RBL-2H3 cells, but may promote the development of relevant strategies for overcoming the adverse effects of the drug.
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
Lufen
L
Huang
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
Ting
T
Li
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China.
Hua
H
Zhou
Hunan Zhengqing Pharmaceutical Group Limited, Huaihua, China.
Ping
P
Qiu
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China. Electronic address: jlwu@must.edu.mo.
Jianlin
J
Wu
State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China. Electronic address: lliu@must.edu.mo.
Liang
L
Liu
D000707:Anaphylaxis / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D001491:Basophils / Q000187:drug effects* / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D004342:Drug Hypersensitivity / Q000150:complications / Q000276:immunology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009019:Morphinans / Q000009:adverse effects / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D032841:Sinomenium / Q000276:immunology
D017305:Annexin A1; D009019:Morphinans; C009271:sinomenine; D054467:Phospholipases A2; D002118:Calcium
Annexin A1; Cytosolic phospholipase A(2); Extracellular signal-regulated kinase; RBL-2H3 basophils; Sinomenine