Dipyridamole Inhibits Lipopolysaccharide-Induced Interleukin-6 Secretion via Activation of Mitogen-Activated Protein Kinase Phosphatase-1 in Rat Mesangial Cells

范 揚智(Yang-Chih Fan), 鄭 仲益(Chung-Yi Cheng), 陳 正憲(Cheng-Hsien Chen), 陳 振文(Tzen-Wen Chen), 陳 作孝(Tso-Hsiao Chen)

Research output: Contribution to journalArticle

Abstract

Background: Dipyridamole, one type of antiplatelet, has been used in a variety of glomerulonephritis to decrease proteinuria or hematuria. Although it could inhibit the proliferation of glomerular mesangial cells (MCs), the precise mechanism involved remained unclear. Our previous studies have shown that dipyridamole had anti-inflammatory effect through activation of mitogen-activated protein kinase phosphotase-1 (MKP-1) in macrophages. Urinary interleukin-6 (IL-6) was related to the severity of glomerulonephritis and it could be produced in mesangial cells. In this study, we investigated the anti-inflammatory effect of dipyridamole on IL-6 secretion, and studied the role of MKP-1 in bacterial lipopolysaccharide (LPS)-stimulated cultured rat mesangial cells (RMCs). Methods: IL-6 secretion from RMCs induced by LPS with and without dipyridamole pretreatment were assessed. LPS-induced reactive oxygen species (ROS) generation was measured using the fluorescent probe dichlorofluorescein. MKP-1 siRNA was also used for MKP-1 gene knockdown for comparison with the control group in this study. Results: Incubation of RMCs with LPS-induced IL-b secretion and pretreated with dipyridamole showed significant inhibition of IL-6 secretion anti ROS generation in a dose-dependent manner. Our results showed that LPS-induced IL-6 secretion in RMCs was dependent on ROS. In addition, dipyridamole inhibited lire LPS-stimulated NF-xB DNA binding activity and the phosphorylation of 1xB. The dipyridamole inhibitory effect on LPS-induced IL-6 secretion was reduced in MKP-1 siRNA knockdown cells. Conclusion: It appears that dipyridamole would exert anti-inflammatory effect via activation of MKP-1 in RMCs.
Translated title of the contributionDipyridamole經由活化分裂素蛋白激酶磷酸酶-1抑制脂多醣體在大鼠腎膈細胞所誘導白細胞介素-6表現
Original languageEnglish
Pages (from-to)33-39
Number of pages7
JournalActa Nephrologica
Volume23
Issue number1
Publication statusPublished - 2009

Keywords

  • dipyridamole
  • mesangial cell
  • interleukin-6
  • mitogen-activated protein kinase phophatase-1

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