| Chen BC |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=3.555 ------>paper_class3=2 ------>paper_class2=1 ------>vol= ------>confirm_bywho=sheujr ------>insert_bywho=aspirin ------>Jurnal_Rank=28.1 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2= ------>medlineContent= ------>unit=E0106 ------>insert_date=20090928 ------>iam=4 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=Mol Immunol ------>paper_name=Rac1 regulates peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the phosphatidylinositol 3-kinase/Akt pathway. ------>confirm_date=20090928 ------>tch_id=095032 ------>pmid=19118901 ------>page1= ------>fullAbstract=Previously, we found that peptidoglycan (PGN), a cell wall component of the gram-positive bacterium Staphylococcus aureus, may activate the Ras/Raf-1/extracellular signal-regulated kinase (ERK) pathway, which in turn initiates IkappaB kinases alpha/beta (IKKalpha/beta) and nuclear factor-kappaB (NF-kappaB) activation, and ultimately induces cyclooxygenase-2 (COX-2) expression in RAW 264.7 macrophages. In this study, we further investigated the roles of Rac1, phosphatidylinositol 3-kinase (PI3K), and Akt in PGN-induced NF-kappaB activation and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 expression was attenuated by a Rac1 dominant negative mutant (RacN17), PI3K inhibitors (wortmannin and LY 294002), and an Akt inhibitor (1L-6-hydroxymethyl-chiro-inositol2-[(R)-2-O-methyl-3-O-octadecylcarbonate ]). PGN-induced PGE(2) release was also inhibited by RacN17. Treatment of RAW 264.7 macrophages with PGN caused the activation of Rac and Akt. PGN-induced Akt activation was inhibited by RacN17, LY 294002, and the Akt inhibitor. Stimulation of RAW 264.7 macrophages with PGN resulted in an increase in IKKalpha/beta phosphorylation and p65 Ser536 phosphorylation; these effects were inhibited by RacN17, LY 294002, an Akt inhibitor, and an Akt dominant negative mutant (AktDN). The PGN-induced increases in kappaB-luciferase activity were also inhibited by RacN17, wortmannin, LY 294002, an Akt inhibitor, and AktDN. Treatment of macrophages with PGN induced the recruitment of p85alpha and Rac1 to Toll-like receptor 2 (TLR2) in a time-dependent manner. These results indicate that PGN may activate the Rac1/PI3K/Akt pathway through the recruitment of p85alpha and Rac1 to TLR2 to mediate IKKalpha/beta activation and p65 phosphorylation, which in turn induces NF-kappaB transactivation, and ultimately causes COX-2 expression in RAW 264.7 macrophages. ------>tmu_sno=None ------>sno=22340 ------>authors2=Kang JC ------>authors3=Lu YT ------>authors4=Hsu MJ ------>authors5=Liao CC ------>authors6=Chiu WT, Yeh FL, Lin CH ------>authors6_c= ------>authors=Chen BC ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Rac1 regulates peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the phosphatidylinositol 3-kinase/Akt pathway. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=1 |