PMID- 18824136 OWN - NLM STAT- MEDLINE DCOM- 20090427 LR - 20091119 IS - 1537-1891 (Print) IS - 1537-1891 (Linking) VI - 50 IP - 1-2 DP - 2009 Jan-Feb TI - TLR-4 agonistic lipopolysaccharide upregulates interleukin-8 at the transcriptional and post-translational level in vascular smooth muscle cells. PG - 34-9 LID - 10.1016/j.vph.2008.08.006 [doi] AB - Despite extensive studies on cellular responses to activation of Toll-like receptor-4 (TLR-4), it is not evident weather its activation affects gene expression of interleukin-8 (IL-8) in vascular smooth muscle cells (VSMCs). Therefore, this study has investigated whether and how TLR-4 influences IL-8 expression in VSMCs. Exposure of aortic smooth muscle cells to TLR-4 agonistic lipopolysaccharide (LPS) not only enhanced release of IL-8 protein but also induced IL-8 gene transcript via promoter activation. The LPS-induced activation of IL-8 promoter was attenuated by dominant-negative MKK1, but not by dominant-negative MKK3. The promoter activation was also impaired by dominant negative CCAAT/enhancer binding protein (C/EBP), IkappaB, and dominant negative c-Jun. In comparison with the mutation of the AP-1 binding site, the mutation of NF-kappaB site and C/EBP binding site in the IL-8 promoter region more significantly impaired the promoter activation. Moreover, both promoter activity and release of IL-8 were inhibited by U0126 and curcumin, but not by SB202190, epigallocatechin 3-gallate and resveratrol. The present study reports that TLR-4-agonistic LPS upregulates IL-8 at the transcriptional and post-translational level in VSMCs, and that ERK1/2, NF-kappaB, and C/EBP play major roles in the upregulation of IL-8. FAU - Hong, Taek-Jong AU - Hong TJ AD - Department of Internal Medicine, School of Medicine-Pusan National University, Busan, Republic of Korea. FAU - Ban, Ji-Eun AU - Ban JE FAU - Choi, Kyung-Ha AU - Choi KH FAU - Son, Yong-Hae AU - Son YH FAU - Kim, Sun-Mi AU - Kim SM FAU - Eo, Seong-Kug AU - Eo SK FAU - Park, Hee-Ju AU - Park HJ FAU - Rhim, Byung-Yong AU - Rhim BY FAU - Kim, Koanhoi AU - Kim K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080913 PL - United States TA - Vascul Pharmacol JT - Vascular pharmacology JID - 101130615 RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (Interleukin-8) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Aorta/cytology/metabolism MH - CCAAT-Enhancer-Binding Proteins/genetics/metabolism MH - Cells, Cultured MH - Humans MH - Interleukin-8/genetics/*metabolism MH - Lipopolysaccharides/pharmacology MH - Muscle, Smooth, Vascular/*metabolism MH - NF-kappa B/genetics MH - Promoter Regions, Genetic MH - RNA Processing, Post-Transcriptional/drug effects MH - RNA, Messenger/metabolism MH - Signal Transduction/drug effects MH - Toll-Like Receptor 4/agonists/*metabolism MH - Transcription, Genetic/drug effects MH - Transcriptional Activation/drug effects MH - Up-Regulation/drug effects MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism EDAT- 2008/10/01 09:00 MHDA- 2009/04/28 09:00 CRDT- 2008/10/01 09:00 PHST- 2008/05/14 00:00 [received] PHST- 2008/08/20 00:00 [revised] PHST- 2008/08/22 00:00 [accepted] PHST- 2008/10/01 09:00 [entrez] PHST- 2008/10/01 09:00 [pubmed] PHST- 2009/04/28 09:00 [medline] AID - S1537-1891(08)00112-2 [pii] AID - 10.1016/j.vph.2008.08.006 [doi] PST - ppublish SO - Vascul Pharmacol. 2009 Jan-Feb;50(1-2):34-9. doi: 10.1016/j.vph.2008.08.006. Epub 2008 Sep 13.