PMID- 21834066
OWN - NLM
STAT- MEDLINE
DCOM- 20130125
LR  - 20111031
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 63
IP  - 11
DP  - 2011 Nov
TI  - Interleukin-17A induction of angiogenesis, cell migration, and cytoskeletal 
      rearrangement.
PG  - 3263-73
LID - 10.1002/art.30582 [doi]
AB  - OBJECTIVE: To examine the ability of interleukin-17A (IL-17A) to stimulate 
      angiogenesis, cell migration, and cytoskeletal rearrangement. METHODS: The effect 
      of IL-17A on microvascular tube formation and extracellular matrix invasion by 
      human dermal endothelial cells (HDECs) was assessed using Matrigel matrix and 
      Transwell Matrigel invasion chambers. IL-17A-induced growth-related oncogene alpha 
      (GROalpha) and monocyte chemotactic protein 1 (MCP-1) production in rheumatoid 
      arthritis synovial fibroblasts (RASFs) and HDECs was measured by enzyme-linked 
      immunosorbent assay. IL-17A-induced migration was assessed using peripheral blood 
      mononuclear cell (PBMC) migration assays and wound-repair scratch assays, with or 
      without anti-GROalpha and anti-MCP-1 antibodies. Binding of beta1 integrin receptors was 
      assessed using integrin binding assays. Cytoskeletal assembly/disassembly in 
      RASFs and HDECs were assessed by immunofluorescence staining for F-actin. 
      IL-17A-induced cell migration and cytoskeletal disassembly were assessed in the 
      presence of a Rac1 inhibitor (NSC23766). Rac1 activation following IL-17 
      stimulation in the presence or absence of anti-GROalpha, anti-MCP-1, or IgG control 
      was assessed by Rac GTPase pull-down assays and Western blotting. RESULTS: IL-17A 
      significantly up-regulated angiogenesis and endothelial cell invasion. It 
      significantly induced GROalpha and MCP-1 expression in RASFs. Migration of PBMCs, 
      RASFs, and HDECs was induced by IL-17A; these effects were blocked by anti-GROalpha 
      or anti-MCP-1 antibodies. IL-17A significantly up-regulated beta1 integrin receptor 
      binding and induced cytoskeletal disassembly in RASFs and HDECs. Rac1 activation 
      was directly induced by IL-17A. IL-17A-induced wound repair and actin 
      rearrangement were inhibited by a pharmacologic inhibitor of Rac1 (NSC23766). 
      Anti-GROalpha or anti-MCP-1 antibodies had no effect on IL-17A-induced Rac1 
      activation. CONCLUSION: IL-17A induces angiogenesis, cell migration, and cell 
      invasion, all of which are key processes in the pathogenesis of rheumatoid 
      arthritis and ones that are mediated in part through chemokine- and 
      cytoskeleton-dependent pathways.
CI  - Copyright (c) 2011 by the American College of Rheumatology.
FAU - Moran, Ellen M
AU  - Moran EM
AD  - Dublin Academic Medical Centre and The Conway Institute of Biomolecular and 
      Biomedical Research, University College Dublin, Dublin, Ireland.
FAU - Connolly, Mary
AU  - Connolly M
FAU - Gao, Wei
AU  - Gao W
FAU - McCormick, Jennifer
AU  - McCormick J
FAU - Fearon, Ursula
AU  - Fearon U
FAU - Veale, Douglas J
AU  - Veale DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Interleukin-17)
SB  - IM
MH  - Arthritis, Rheumatoid/*metabolism/pathology
MH  - Cell Movement/drug effects/*physiology
MH  - Cytoskeleton/drug effects/*metabolism/pathology
MH  - Fibroblasts/drug effects/metabolism/pathology
MH  - Humans
MH  - Interleukin-17/*metabolism/pharmacology
MH  - Neovascularization, Physiologic/drug effects/*physiology
MH  - Synovial Membrane/drug effects/metabolism/pathology
EDAT- 2011/08/13 06:00
MHDA- 2013/01/26 06:00
CRDT- 2011/08/12 06:00
PHST- 2011/08/12 06:00 [entrez]
PHST- 2011/08/13 06:00 [pubmed]
PHST- 2013/01/26 06:00 [medline]
AID - 10.1002/art.30582 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2011 Nov;63(11):3263-73. doi: 10.1002/art.30582.