PMID- 20051654
OWN - NLM
STAT- MEDLINE
DCOM- 20100916
LR  - 20190911
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 112
IP  - 1
DP  - 2010
TI  - Possible involvements of nuclear factor-kappa B and activator protein-1 in the 
      tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase-12 
      in human alveolar epithelial A549 cell line.
PG  - 83-8
AB  - Matrix metalloproteinase-12 (MMP-12) has been suggested to play an important role 
      in airway inflammatory diseases. Tumor necrosis factor-alpha (TNF-alpha) is known 
      to cause an upregulation of MMP-12 via an activation of activator protein-1 
      (AP-1) in monocytes. In the present study, we investigated the effect of 
      TNF-alpha on the expressions of MMP-12 in airway epithelial cells, one of the 
      sources of MMP-12 in the airway, and its underlying mechanism. MMP-12 mRNA and 
      protein expressions induced by TNF-alpha in the absence or presence of BMS-345541 
      (a selective IkappaB kinase inhibitor) or SP600125 [a selective c-Jun N-terminal 
      kinase (JNK) inhibitor] were measured by quantitative real-time PCR and Western 
      blotting, respectively. Furthermore, siRNAs for p65 and JNK2 were used to confirm 
      the involvements of nuclear factor-kappaB (NF-kappaB) and AP-1 in the MMP-12 mRNA 
      expression induced by TNF-alpha in A549 cells. Both MMP-12 mRNA and protein were 
      upregulated by the treatment with TNF-alpha in time- and concentration-dependent 
      manners. Both BMS-345541 and SP600125 inhibited the upregulation of MMP-12 
      induced by TNF-alpha. Furthermore, both the depletion of p65 and JNK2 by siRNAs 
      significantly attenuated the upregulation of MMP-12 induced by TNF-alpha. These 
      findings suggest that both NF-kappaB and JNK / AP-1 pathways are important for 
      the MMP-12 upregulation induced by TNF-alpha in A549 cells.
FAU - Yu, Yingyan
AU  - Yu Y
AD  - Department of Pharmacology, School of Pharmacy, Hoshi University, Japan.
FAU - Chiba, Yoshihiko
AU  - Chiba Y
FAU - Sakai, Hiroyasu
AU  - Sakai H
FAU - Misawa, Miwa
AU  - Misawa M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20100106
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.65 (Matrix Metalloproteinase 12)
SB  - IM
MH  - Cell Line, Tumor
MH  - Humans
MH  - Matrix Metalloproteinase 12/*biosynthesis
MH  - NF-kappa B/*biosynthesis
MH  - Pulmonary Alveoli/enzymology/*metabolism
MH  - Respiratory Mucosa/enzymology/*metabolism
MH  - Signal Transduction/physiology
MH  - Transcription Factor AP-1/*biosynthesis
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - Up-Regulation/*physiology
EDAT- 2010/01/07 06:00
MHDA- 2010/09/18 06:00
CRDT- 2010/01/07 06:00
PHST- 2010/01/07 06:00 [entrez]
PHST- 2010/01/07 06:00 [pubmed]
PHST- 2010/09/18 06:00 [medline]
AID - JST.JSTAGE/jphs/09268FP [pii]
AID - 10.1254/jphs.09268fp [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2010;112(1):83-8. doi: 10.1254/jphs.09268fp. Epub 2010 Jan 6.