PMID- 22406061
OWN - NLM
STAT- MEDLINE
DCOM- 20120516
LR  - 20211021
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 420
IP  - 1
DP  - 2012 Mar 30
TI  - A pro-inflammatory role of deubiquitinating enzyme cylindromatosis (CYLD) in 
      vascular smooth muscle cells.
PG  - 78-83
LID - 10.1016/j.bbrc.2012.02.118 [doi]
AB  - CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse 
      cellular processes, ranging from proliferation and differentiation to 
      inflammatory responses, via regulating multiple key signaling cascades such as 
      nuclear factor kappa B (NF-kappaB) pathway. CYLD has been shown to inhibit vascular 
      lesion formation presumably through suppressing NF-kappaB activity in vascular cells. 
      However, herein we report a novel role of CYLD in mediating pro-inflammatory 
      responses in vascular smooth muscle cells (VSMCs) via a mechanism independent of 
      NF-kappaB activity. Adenoviral knockdown of Cyld inhibited basal and the tumor 
      necrosis factor alpha (TNFalpha)-induced mRNA expression of pro-inflammatory 
      cytokines including monocyte chemotactic protein-1 (Mcp-1), intercellular 
      adhesion molecule (Icam-1) and interleukin-6 (Il-6) in rat adult aortic SMCs 
      (RASMCs). The CYLD deficiency led to increases in the basal NF-kappaB transcriptional 
      activity in RASMCs; however, did not affect the TNFalpha-induced NF-kappaB activity. 
      Intriguingly, the TNFalpha-induced IkappaB phosphorylation was enhanced in the CYLD 
      deficient RASMCs. While knocking down of Cyld decreased slightly the basal 
      expression levels of IkappaBalpha and IkappaBbeta proteins, it did not alter the kinetics of 
      TNFalpha-induced IkappaB protein degradation in RASMCs. These results indicate that CYLD 
      suppresses the basal NF-kappaB activity and TNFalpha-induced IkappaB kinase activation 
      without affecting TNFalpha-induced NF-kappaB activity in VSMCs. In addition, knocking 
      down of Cyld suppressed TNFalpha-induced activation of mitogen activated protein 
      kinases (MAPKs) including extracellular signal-activated kinases (ERK), c-Jun 
      N-terminal kinase (JNK), and p38 in RASMCs. TNFalpha-induced RASMC migration and 
      monocyte adhesion to RASMCs were inhibited by the Cyld knockdown. Finally, 
      immunochemical staining revealed a dramatic augment of CYLD expression in the 
      injured coronary artery with neointimal hyperplasia. Taken together, our results 
      uncover an unexpected role of CYLD in promoting inflammatory responses in VSMCs 
      via a mechanism involving MAPK activation but independent of NF-kappaB activity, 
      contributing to the pathogenesis of vascular disease.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Liu, Shuai
AU  - Liu S
AD  - Shandong University Qilu Hospital Research Center for Cell Therapy, Key 
      Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of 
      Shandong University, Jinan 250012, China.
FAU - Lv, Jiaju
AU  - Lv J
FAU - Han, Liping
AU  - Han L
FAU - Ichikawa, Tomonaga
AU  - Ichikawa T
FAU - Wang, Wenjuan
AU  - Wang W
FAU - Li, Siying
AU  - Li S
FAU - Wang, Xing Li
AU  - Wang XL
FAU - Tang, Dongqi
AU  - Tang D
FAU - Cui, Taixing
AU  - Cui T
LA  - eng
GR  - P20 GM103499/GM/NIGMS NIH HHS/United States
GR  - P20 GM103499-12/GM/NIGMS NIH HHS/United States
GR  - P20 RR016461/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120301
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.1.27.5 (Ang2 protein, mouse)
RN  - EC 3.1.27.5 (Ribonuclease, Pancreatic)
RN  - EC 3.4.19.12 (CYLD protein, mouse)
RN  - EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Animals
MH  - Arteritis/*enzymology/pathology
MH  - Cell Adhesion
MH  - Cell Movement/drug effects/physiology
MH  - Coronary Vessels/enzymology/pathology
MH  - Cysteine Endopeptidases/genetics/*physiology
MH  - Deubiquitinating Enzyme CYLD
MH  - Gene Knockdown Techniques
MH  - Hyperplasia/enzymology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Monocytes/enzymology/physiology
MH  - Muscle, Smooth, Vascular/*enzymology/pathology
MH  - Myocytes, Smooth Muscle/*enzymology/pathology
MH  - NF-kappa B/metabolism
MH  - Neointima/enzymology/pathology
MH  - Ribonuclease, Pancreatic/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation
PMC - PMC3920579
MID - NIHMS360895
EDAT- 2012/03/13 06:00
MHDA- 2012/05/17 06:00
PMCR- 2014/02/11
CRDT- 2012/03/13 06:00
PHST- 2012/02/16 00:00 [received]
PHST- 2012/02/18 00:00 [accepted]
PHST- 2012/03/13 06:00 [entrez]
PHST- 2012/03/13 06:00 [pubmed]
PHST- 2012/05/17 06:00 [medline]
PHST- 2014/02/11 00:00 [pmc-release]
AID - S0006-291X(12)00377-4 [pii]
AID - 10.1016/j.bbrc.2012.02.118 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Mar 30;420(1):78-83. doi: 
      10.1016/j.bbrc.2012.02.118. Epub 2012 Mar 1.