| Chen TH |
------>authors3_c=??? ------>paper_class1=1 ------>Impact_Factor=2.477 ------>paper_class3=2 ------>paper_class2=1 ------>vol=541 ------>confirm_bywho=leehorng ------>insert_bywho=leehorng ------>Jurnal_Rank=32.6 ------>authors4_c=??? ------>comm_author=1 ------>patent_EDate=None ------>authors5_c=??? ------>publish_day=1 ------>paper_class2Letter=None ------>page2=146 ------>medlineContent= ------>unit=E0600 ------>insert_date=20061003 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c=??? ------>score=500 ------>journal_name=European Journal of Pharmacology ------>paper_name=Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells ------>confirm_date=20061003 ------>tch_id=081004 ------>pmid=16765938 ------>page1=138 ------>fullAbstract=Dipyridamole is a nucleoside transport inhibitor and a non-selective phosphodiesterase inhibitor. However, the mechanisms by which dipyridamole exerts its anti-inflammatory effects are not completely understood. In the present study, we investigated the role of mitogen-activated kinase phosphatase-1 (MKP-1) in dipyridamole~s anti-inflammatory effects. We show that dipyridamole inhibited interleukin-6 and monocyte chemoattractant protein-1 secretion, inducible nitric oxide synthase protein expression, nitrite accumulation, and cyclooxygenase-2 (COX-2) induction in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Dipyridamole inhibited the nuclear factor kappa B (NF-kappaB) signaling pathway as demonstrated by inhibition of the inhibitor of NF-kappaB (IkappaB) phosphorylation, IkappaB degradation, p65 translocation from the cytosol to the nucleus, and transcription of the reporter gene. Dipyridamole also inhibited LPS-stimulated p38 mitogen-activated protein kinase (p38 MAPK) and IkappaB kinase-beta (IKK-beta) activities in RAW 264.7 cells. A p38 MAPK inhibitor, SB 203580, inhibited LPS-stimulated COX-2 expression and IKK-beta activation suggesting that LPS may activate the NF-kappaB signaling pathway via upstream p38 MAPK activation. Furthermore, dipyridamole stimulated transient activation of MKP-1, a potent inhibitor of p38 MAPK function. Knockdown of MKP-1 by transfecting MKP-1 siRNA or inhibition of MKP-1 by the specific inhibitor, triptolide, significantly reduced the inhibitory effects of dipyridamole on COX-2 expression induced by LPS. Taken together, these data suggest that dipyridamole exerts its anti-inflammatory effect via activation of MKP-1, which dephosphorylates and inactivates p38 MAPK. Inactivation of p38 MAPK in turn inhibits IKK-beta activation and subsequently the NF-kappaB signaling pathway that mediates LPS-induced cyclooxygenase-2 expression in RAW 264.7 cells. ------>tmu_sno=None ------>sno=14122 ------>authors2=Kao YC ------>authors3=Chen BC ------>authors4=Chen CH ------>authors5=Chan P ------>authors6=Lee HM ------>authors6_c=??? ------>authors=Chen TH ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=??? ------>publish_area=0 ------>updateTitle=Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2006 ------>submit_flag=None ------>publish_month=1 |