PMID- 19602845
OWN - NLM
STAT- MEDLINE
DCOM- 20091015
LR  - 20190911
IS  - 1347-8613 (Print)
IS  - 1347-8613 (Linking)
VI  - 110
IP  - 4
DP  - 2009 Aug
TI  - Tumor necrosis factor-alpha (TNF-alpha) induces upregulation of RhoA via 
      NF-kappaB activation in cultured human bronchial smooth muscle cells.
PG  - 437-44
AB  - RhoA plays an important role in Ca(2+) sensitization of bronchial smooth muscle 
      in antigen-induced airway hyperresponsiveness (AHR). Tumor necrosis factor-alpha 
      (TNF-alpha), a major proinflammatory cytokine, is capable of inducing AHR, but 
      the mechanisms for this are still unknown. In the present study, the effect of 
      TNF-alpha on RhoA protein expression was examined in cultured human bronchial 
      smooth muscle cells (hBSMCs). To investigate the role of NF-kappaB in the 
      TNF-alpha-induced upregulation of RhoA, the effects of an inhibitor of IkappaB 
      kinase (IKK), BMS-345541, were also determined. Both immunoblot and 
      immunocytochemical analyses revealed that incubation of the hBSMCs with TNF-alpha 
      caused an activation of NF-kappaB (determined by a translocation of p65 proteins 
      to nuclei): the peak response was observed when cells were incubated with 10 
      ng/mL of TNF-alpha for 30 min. An upregulation of RhoA protein was also observed 
      at 12 - 24 h after the incubation with TNF-alpha (10 ng/mL). Both the activation 
      of NF-kappaB and upregulation of RhoA were concentration-dependently inhibited by 
      the co-incubation with BMS-345541. These results suggest that TNF-alpha-induced 
      upregulation of RhoA might be mediated by an activation of NF-kappaB in hBSMCs.
FAU - Goto, Kumiko
AU  - Goto K
AD  - Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, 
      Shinagawa-ku, Tokyo, Japan.
FAU - Chiba, Yoshihiko
AU  - Chiba Y
FAU - Sakai, Hiroyasu
AU  - Sakai H
FAU - Misawa, Miwa
AU  - Misawa M
LA  - eng
PT  - Journal Article
DEP - 20090714
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline)
RN  - 0 (Imidazoles)
RN  - 0 (NF-kappa B)
RN  - 0 (Quinoxalines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Bronchi/cytology/metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Imidazoles/administration & dosage/pharmacology
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Myocytes, Smooth Muscle/metabolism
MH  - NF-kappa B/*metabolism
MH  - Quinoxalines/administration & dosage/pharmacology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
MH  - Up-Regulation
MH  - rhoA GTP-Binding Protein/*genetics/metabolism
EDAT- 2009/07/16 09:00
MHDA- 2009/10/16 06:00
CRDT- 2009/07/16 09:00
PHST- 2009/07/16 09:00 [entrez]
PHST- 2009/07/16 09:00 [pubmed]
PHST- 2009/10/16 06:00 [medline]
AID - JST.JSTAGE/jphs/09081FP [pii]
AID - 10.1254/jphs.09081fp [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2009 Aug;110(4):437-44. doi: 10.1254/jphs.09081fp. Epub 2009 Jul 
      14.