Chen BC |
------>authors3_c=??? ------>paper_class1=1 ------>Impact_Factor=5.581 ------>paper_class3=2 ------>paper_class2=1 ------>vol=284 ------>confirm_bywho=chshih43 ------>insert_bywho=bcchen ------>Jurnal_Rank=15.2 ------>authors4_c=??? ------>comm_author= ------>patent_EDate=None ------>authors5_c=??? ------>publish_day=31 ------>paper_class2Letter=None ------>page2=20573 ------>medlineContent= ------>unit=E0400 ------>insert_date=20090702 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c=??? ------>score=488 ------>journal_name=The Journal of Biological Chemistry ------>paper_name=Peptidoglycan induces cyclooxygenase-2 expression in macrophages by activating the neutral sphinomylinase-ceramide pathway ------>confirm_date=20090825 ------>tch_id=091057 ------>pmid=19531467 ------>page1=20562 ------>fullAbstract=The sphingomyelin signal transduction pathway is known to play a role in mediating the action of various cytokines. Herein, we examined the role of neutral sphingomyelinase (nSMase)/ceramide in peptidoglycan (PGN)-induced NF-kappaB activation and cyclooxygenase-2 (COX-2) expression in macrophages. PGN-induced COX-2 expression was attenuated by an nSMase inhibitor (3-O-methyl-sphingomyeline, 3-OMS) and ceramidase, but not by an acidic SMase inhibitor (imipramine). C2-ceramide, bacterial SMase (which mimics cellular SMase activity), and a ceramidase inhibitor (N-oleoyl-ethanolamine) individually had no effect on COX-2 expression; however, they markedly enhanced PGN-induced COX-2 expression. PGN activated nSMase, but not acidic SMase, resulting in increased ceramide generation. PGN-induced nSMase activation and ceramide formation were inhibited by 3-OMS, but not by imipramine. PGN-induced COX-2 expression was inhibited by a p38 MAPK inhibitor (SB 203580) and dominant negative mutants of MAPK kinase (MKK) 3, MKK6, and p38 MAPKalpha. 3-OMS selectively inhibited PGN-induced p38 MAPK and MKK3/6 activation, but not JNK or ERK1/2. C2-ceramide, bacterial SMase, and N-oleoyl-ethanolamine all induced p38 MAPK or MKK3/6 activation. The PGN-mediated increases in kappaB-luciferase activity were also inhibited by 3-OMS and the p38 MAPKalphaDN, but not by imipramine. Furthermore, C2-ceramide caused an increase in kappaB-luciferase activity. Our data demonstrate for the first time that PGN activates the nSMase/ceramide pathway to induce MKK3/6/p38 MAPK activation, which in turn initiates NF-kappaB activation and ultimately induces COX-2 expression in macrophages. The nSMase/ceramide pathway is required but might not be sufficient for COX-2 expression induced by PGN. ------>tmu_sno=None ------>sno=22002 ------>authors2=Chang HM ------>authors3=Hsu MJ ------>authors4=Shih CM ------>authors5=Chiu YH ------>authors6=Chiu WT, Lin CH ------>authors6_c=???,??? ------>authors=Chen BC ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=??? ------>publish_area=0 ------>updateTitle=Peptidoglycan induces cyclooxygenase-2 expression in macrophages by activating the neutral sphingomyelinase-ceramide pathway. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=31 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=7 |