PMID- 11728452 OWN - NLM STAT- MEDLINE DCOM- 20011226 LR - 20190621 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 508 IP - 3 DP - 2001 Nov 23 TI - NF-kappaB is required for TNF-alpha-directed smooth muscle cell migration. PG - 360-4 AB - Migration of vascular smooth muscle cells (VSMC) is a crucial event in the formation of vascular stenotic lesions. Tumor necrosis factor-alpha (TNF-alpha) is elaborated by VSMC in atherosclerosis and following angioplasty. We investigated the role of nuclear factor-kappaB (NF-kappaB) in human VSMC migration induced by TNF-alpha. Adenoviral expression of a mutant form of the inhibitor of NF-kappaB, IkappaB-alphaM, suppressed TNF-alpha-triggered degradation of cellular IkappaB-alpha, inhibited activation of NF-kappaB, and attenuated TNF-alpha-induced migration. Further, IkappaB-alphaM suppressed TNF-alpha-stimulated release of interleukin-6 and -8 (IL-6 and IL-8). Neutralization of IL-6 and IL-8 with appropriate antibodies reduced TNF-alpha-induced VSMC migration. Addition of recombinant IL-6 and IL-8 stimulated migration. Collectively, our data provide initial evidence that TNF-alpha-mediated VSMC migration requires NF-kappaB activation and is associated with induction of IL-6 and IL-8 which act in an autocrine manner. FAU - Wang, Z AU - Wang Z AD - Division of Basic Medical Science, Mercer University School of Medicine, Macon, GA 31207, USA. wang_z@mercer.edu FAU - Castresana, M R AU - Castresana MR FAU - Newman, W H AU - Newman WH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (DNA-Binding Proteins) RN - 0 (I-kappa B Proteins) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (NF-kappa B) RN - 0 (NFKBIA protein, human) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - 1CC1JFE158 (Dactinomycin) RN - 98600C0908 (Cycloheximide) SB - IM MH - Adenoviridae/genetics MH - Autocrine Communication MH - Cell Movement MH - Cells, Cultured MH - *Chemotaxis MH - Cycloheximide/pharmacology MH - DNA-Binding Proteins/genetics/metabolism MH - Dactinomycin/pharmacology MH - Genetic Vectors MH - Humans MH - *I-kappa B Proteins MH - Interleukin-6/genetics/metabolism/pharmacology MH - Interleukin-8/genetics/metabolism/pharmacology MH - Muscle, Smooth, Vascular/*cytology/*metabolism MH - NF-KappaB Inhibitor alpha MH - NF-kappa B/*metabolism MH - Nucleic Acid Synthesis Inhibitors/pharmacology MH - Protein Synthesis Inhibitors/pharmacology MH - RNA, Messenger/genetics/metabolism MH - Recombinant Proteins/metabolism/pharmacology MH - Tumor Necrosis Factor-alpha/*pharmacology/physiology EDAT- 2001/12/01 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/12/01 10:00 PHST- 2001/12/01 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/12/01 10:00 [entrez] AID - S0014-5793(01)03109-X [pii] AID - 10.1016/s0014-5793(01)03109-x [doi] PST - ppublish SO - FEBS Lett. 2001 Nov 23;508(3):360-4. doi: 10.1016/s0014-5793(01)03109-x.