PMID- 23816956 OWN - NLM STAT- MEDLINE DCOM- 20140218 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 31 IP - 6 DP - 2013 TI - Oxidized low-density lipoprotein induces inflammatory responses in cultured human mast cells via Toll-like receptor 4. PG - 842-53 LID - 10.1159/000350102 [doi] AB - BACKGROUND/AIMS: Oxidized low-density lipoprotein (ox-LDL) is a powerful atherogen. Toll-like receptor 4 (TLR4) has a pathophysiological role in regulating inflammatory responses and atherosclerosis. Mast cells can infiltrate into the atheromatous plaque and secrete various pro-inflammatory cytokines, which significantly amplify the atherogenic processes and promote plaque vulnerability. Small interfering RNA (siRNA) is an effective method to silence the target genes. We evaluated whether ox-LDL-induced inflammation depended in part on the activation of TLR4-dependent signaling pathways in a cultured human mast cell line (HMC-1). METHOD: HMC-1 cells were cultured, and treated with ox-LDL, TLR4-specific siRNA, or inhibitors of phosphorylation of mitogen-activated protein kinase (MAPKs), and nuclear factor-kappaB (NF-kappaB), a critical mediator of inflammation. The expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) was measured subsequently. RESULTS: Ox-LDL increased the expression of TLR4 and secretion of MCP-1, TNF-alpha and IL-6. Moreover, ox-LDL stimulated the translocation of NF-kappaB, from the cytoplasm to nucleus. Additionally, phosphorylation of MAPK was greatly increased. These ox-LDL-induced alterations were significantly attenuated by pretreatment with TLR4-specific siRNA. CONCLUSION: Ox-LDL induced inflammatory responses in cultured HMC-1 cells including NF-kappaB nuclear translocation and phosphorylation of MAPKs, a process mediated in part by TLR4. CI - Copyright (c) 2013 S. Karger AG, Basel. FAU - Meng, Zhe AU - Meng Z AD - Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China. mengzhenihao@163.com FAU - Yan, Chao AU - Yan C FAU - Deng, Qian AU - Deng Q FAU - Dong, Xin AU - Dong X FAU - Duan, Zong-Ming AU - Duan ZM FAU - Gao, Deng-Feng AU - Gao DF FAU - Niu, Xiao-Lin AU - Niu XL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130607 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Chemokine CCL2) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Lipoproteins, LDL) RN - 0 (NF-kappa B) RN - 0 (RNA, Small Interfering) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (oxidized low density lipoprotein) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Cells, Cultured MH - Chemokine CCL2/genetics/metabolism MH - Humans MH - Inflammation Mediators/*metabolism MH - Interleukin-6/genetics/metabolism MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - Lipoproteins, LDL/*pharmacology MH - Mast Cells/cytology/*drug effects/metabolism MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism MH - NF-kappa B/antagonists & inhibitors/metabolism MH - Phosphorylation/drug effects MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - Toll-Like Receptor 4/antagonists & inhibitors/genetics/*metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2013/07/03 06:00 MHDA- 2014/02/19 06:00 CRDT- 2013/07/03 06:00 PHST- 2013/05/14 00:00 [accepted] PHST- 2013/07/03 06:00 [entrez] PHST- 2013/07/03 06:00 [pubmed] PHST- 2014/02/19 06:00 [medline] AID - 000350102 [pii] AID - 10.1159/000350102 [doi] PST - ppublish SO - Cell Physiol Biochem. 2013;31(6):842-53. doi: 10.1159/000350102. Epub 2013 Jun 7.