| Ho SC |
------>authors3_c=??? ------>paper_class1=1 ------>Impact_Factor=6.000 ------>paper_class3=2 ------>paper_class2=1 ------>vol=183 ------>confirm_bywho=chshih43 ------>insert_bywho=bcchen ------>Jurnal_Rank=13.2 ------>authors4_c=??? ------>comm_author= ------>patent_EDate=None ------>authors5_c=Ito K ------>publish_day=1 ------>paper_class2Letter=None ------>page2=420 ------>medlineContent= ------>unit=E0400 ------>insert_date=20090825 ------>iam=7 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c=??? ------>score=445 ------>journal_name=Journal of Immunology ------>paper_name=Neutrophil elastase represses IL-8/CXCL8 synthesis in human airway smooth muscle cells through induction of NF-kB repressing factor ------>confirm_date=20090825 ------>tch_id=091057 ------>pmid=19542452 ------>page1=411 ------>fullAbstract=NF-kappaB repressing factor (NRF), a nuclear inhibitor of NF-kappaB, is constitutively expressed and is implicated in the basal silencing of specific NF-kappaB targeting genes, including IFN-beta, IL-8/CXCL8, and iNOS. Little is known about the regulation of NRF and its role in response to stimuli. Airway smooth muscle (ASM) is a rich source of inflammatory mediators that may regulate the development and progression of airway inflammation. We have previously reported that NE activates NF-kappaB in primary human ASM (hASM), leading to induction of TGF-beta1. In this study, we describe that, instead of inducing the NF-kappaB response gene IL-8/CXCL8, NE suppressed IL-8/CXCL8 release and mRNA expression in hASM cells. Transcriptional blockade studies using actinomycin D revealed a similar degradation rate of IL-8/CXCL8 mRNA in the presence or absence of NE, suggesting an involvement at the transcription level. Mechanistically, the NE repressive effect was mediated by inducing NRF, as shown by RT-PCR and Western blotting, which was subsequently recruited to the native IL-8/CXCL8 promoter leading to removal of RNA polymerase II from the promoter, as demonstrated by chromatin immunoprecipitation assays. Knockdown of NRF by small interfering RNA prevented NE-induced suppression of IL-8/CXCL8 expression. In contrast, NE did not induce NRF expression in A549 and Beas-2B cells, where NE only stimulates NF-kappaB activation and IL-8/CXCL8 induction. Forced expression of NRF in A549 cells by an NRF expression plasmid suppressed IL-8/CXCL8 expression. Hence, we describe a novel negative regulatory mechanism of NE-induced NRF, which is restricted to hASM and mediates the suppression of IL-8/CXCL8 expression. ------>tmu_sno=None ------>sno=22134 ------>authors2=Lee KY ------>authors3=Chan YF ------>authors4=Kuo LW ------>authors5=Ito K ------>authors6=Adcock IM, Chen BC, Sheu JR, Lin CH, Kuo HP ------>authors6_c=Adcock IM, ???,???,???,??? ------>authors=Ho SC ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=??? ------>publish_area=0 ------>updateTitle=Neutrophil elastase represses IL-8/CXCL8 synthesis in human airway smooth muscle cells through induction of NF-kappa B repressing factor. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=1 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=7 |