PMID- 24028188
OWN - NLM
STAT- MEDLINE
DCOM- 20140409
LR  - 20211021
IS  - 1529-8027 (Electronic)
IS  - 1085-9489 (Print)
IS  - 1085-9489 (Linking)
VI  - 18
IP  - 3
DP  - 2013 Sep
TI  - Cdc42 GTPases facilitate TNF-alpha-mediated secretion of CCL2 from peripheral nerve 
      microvascular endoneurial endothelial cells.
PG  - 199-208
LID - 10.1111/jns5.12032 [doi]
AB  - Trafficking of autoreactive leukocytes across the blood-nerve barrier and into 
      peripheral nerves is an early pathological hallmark of Guillain-Barre syndrome 
      (GBS). Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, promotes 
      transendothelial migration by upregulating endothelial expression of inflammatory 
      mediators, including CCL2, a chemokine implicated in GBS. We sought to determine 
      the mechanism by which TNF-alpha induces expression and secretion of CCL2 from 
      peripheral nerve microvascular endoneurial endothelial cells (PNMECs). Expression 
      of CCL2 mRNA and protein in quiescent PNMEC cultures was minimal. In contrast, 
      cultures treated with TNF-alpha exhibited increased CCL2 mRNA and protein content, as 
      well as protein secretion. Simvastatin significantly attenuated TNF-alpha-induced 
      CCL2 secretion without affecting CCL2 mRNA or protein expression. Co-incubation 
      with geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate, prevented the 
      effect of simvastatin. By comparison, inhibiting protein isoprenylation with 
      GGTI-298, but not FTI-277, mimicked the effect of simvastatin and significantly 
      attenuated transendothelial migration in vitro. Inhibition of the monomeric 
      GTPase Cdc42, but not Rac1 or RhoA-C, attenuated TNF-alpha-mediated CCL2 secretion. 
      TNF-alpha-mediated trafficking of autoreactive leukocytes into peripheral nerves 
      during GBS may proceed by a mechanism that involves Cdc42-facilitated secretion 
      of CCL2.
CI  - Published 2013. This article is a U.S. Government work and is in the public 
      domain in the USA.
FAU - Langert, Kelly A
AU  - Langert KA
AD  - Research Service, Department of Veterans Affairs, Edward Hines, Jr. VA Hospital, 
      Hines, IL, USA; Program of Neuroscience.
FAU - Von Zee, Cynthia L
AU  - Von Zee CL
FAU - Stubbs, Evan B Jr
AU  - Stubbs EB Jr
LA  - eng
GR  - R03 NS061033/NS/NINDS NIH HHS/United States
GR  - 1R03NS061033/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Peripher Nerv Syst
JT  - Journal of the peripheral nervous system : JPNS
JID - 9704532
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Polyisoprenyl Phosphates)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - N21T0D88LX (geranylgeranyl pyrophosphate)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology
MH  - Leukemia, Monocytic, Acute/pathology
MH  - Peripheral Nerves/*cytology
MH  - Polyisoprenyl Phosphates/pharmacology
MH  - Prenylation/drug effects
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Transendothelial and Transepithelial Migration/drug effects
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - cdc42 GTP-Binding Protein/genetics/*metabolism
PMC - PMC3785369
MID - NIHMS511666
OTO - NOTNLM
OT  - GTPases
OT  - cytokine
OT  - endothelial
OT  - microvascular
OT  - peripheral nerve
EDAT- 2013/09/14 06:00
MHDA- 2014/04/10 06:00
PMCR- 2014/09/01
CRDT- 2013/09/14 06:00
PHST- 2013/02/07 00:00 [received]
PHST- 2013/05/01 00:00 [revised]
PHST- 2013/07/22 00:00 [accepted]
PHST- 2013/09/14 06:00 [entrez]
PHST- 2013/09/14 06:00 [pubmed]
PHST- 2014/04/10 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1111/jns5.12032 [doi]
PST - ppublish
SO  - J Peripher Nerv Syst. 2013 Sep;18(3):199-208. doi: 10.1111/jns5.12032.