PMID- 26884859 OWN - NLM STAT- MEDLINE DCOM- 20161031 LR - 20181113 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 8 IP - 12 DP - 2015 TI - IVIG inhibits TNF-alpha-induced MMP9 expression and activity in monocytes by suppressing NF-kappaB and P38 MAPK activation. PG - 15879-86 AB - Matrix metalloproteinase-9 (MMP9) has been involved in inflammatory and pathologic processes of coronary artery lesions (CAL) in Kawasaki disease (KD). Intravenous immunoglobulin (IVIG), a traditional treatment for Kawasaki disease, could decrease the expressions of MMP9. The purpose of this study was to investigate the protective effect of IVIG in chemotactic migration of monocyte and the regulation of MMP9 induced by tumor necrosis factor-alpha (TNF-alpha) in U937s. Studies were carried out with real time polymerase chain reaction (RT-PCR), zymographic, Western blotting and immunofluorescence. U937s' migration was enhanced by TNF-alpha stimulation, while was inhibited by IVIG pretreatment. MMP9 expression and activity in U937s were also significantly enhanced by TNF-alpha and inhibited by IVIVG pretreatment. During inflammatory stimulus, nuclear factor kappa B (NF-kappaB) and P38 Mitogenactivated protein kinase (P38 MAPK) pathways play a significant role in regulating MMP9 gene expression. TNF-alpha induced nuclear translocation of NF-kappaB and P38 MAPK activation in U937s were inhibited significantly by IVIG. Furthermore, we clarified that nuclear NF-kappaB and P38 MAPK pathways play pivotal roles in regulating U937s' migration and MMP9 expressions using PDTC and SB203580, which were specific inhibitors of NF-kappaB and p38 MAPK pathways. IVIG displays striking biological effects, notably promoting monocyte migration. These effects involve the NF-kappaB and p38 pathways, and increased MMP9 activity. It might be a crucial mechanism of IVIG reducing the occurrence of CAL that IVIG inhibited monocytes expressing MMP9 and decreased chemotactic migration of monocyte. FAU - Zhou, Cuizhen AU - Zhou C AD - Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University Shanghai 200062, China. FAU - Huang, Min AU - Huang M AD - Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University Shanghai 200062, China. FAU - Xie, Lijian AU - Xie L AD - Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University Shanghai 200062, China. FAU - Shen, Jie AU - Shen J AD - Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University Shanghai 200062, China. FAU - Xiao, Tingting AU - Xiao T AD - Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University Shanghai 200062, China. FAU - Wang, Renjian AU - Wang R AD - Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University Shanghai 200062, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151201 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (NF-kappa B) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Anti-Inflammatory Agents/*pharmacology MH - Chemotaxis/drug effects MH - Enzyme Activation MH - Gene Expression Regulation, Enzymologic MH - Humans MH - Immunoglobulins, Intravenous/*pharmacology MH - Matrix Metalloproteinase 9/genetics/*metabolism MH - Monocytes/*drug effects/enzymology MH - NF-kappa B/antagonists & inhibitors/*metabolism MH - Protein Kinase Inhibitors/pharmacology MH - Signal Transduction/drug effects MH - Time Factors MH - Tumor Necrosis Factor-alpha/*pharmacology MH - U937 Cells MH - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism PMC - PMC4730072 OTO - NOTNLM OT - IVIG OT - MMP9 OT - NF-kappaB OT - P38 MAPK OT - monocyte migration EDAT- 2016/02/18 06:00 MHDA- 2016/11/01 06:00 PMCR- 2015/12/01 CRDT- 2016/02/18 06:00 PHST- 2015/10/02 00:00 [received] PHST- 2015/11/25 00:00 [accepted] PHST- 2016/02/18 06:00 [entrez] PHST- 2016/02/18 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] PHST- 2015/12/01 00:00 [pmc-release] PST - epublish SO - Int J Clin Exp Pathol. 2015 Dec 1;8(12):15879-86. eCollection 2015.