PMID- 20649564
OWN - NLM
STAT- MEDLINE
DCOM- 20101130
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 160
IP  - 7
DP  - 2010 Aug
TI  - IL-1beta induces expression of matrix metalloproteinase-9 and cell migration via 
      a c-Src-dependent, growth factor receptor transactivation in A549 cells.
PG  - 1595-610
LID - 10.1111/j.1476-5381.2010.00858.x [doi]
AB  - BACKGROUND AND PURPOSE: Interleukin (IL)-1beta-induced matrix metalloproteinase 
      (MMP-9) expression is regulated by mitogen activated protein kinases (MAPKs) and 
      NF-kappaB. IL-1beta also stimulates transactivation of growth factor receptors 
      and phosphatidylinositol 3-kinase (PI3K)/Akt., leading to the expression of 
      inflammatory proteins. Here, we investigated whether these transactivation 
      mechanisms participated in IL-1beta-induced MMP-9 expression in A549 cells. 
      EXPERIMENTAL APPROACH: A549 cells were treated with/without pharmacological 
      inhibitors and neutralizing antibody or transfected with dominant negative 
      mutants and siRNA of particular protein kinases before stimulation with IL-1beta. 
      Cell migration was measured by in vitro scratch assay. Expression and enzymatic 
      activity of MMP-9 were analysed by Western blot and gelatin zymography. 
      Transcriptional activity of MMP-9 was analysed by RT-PCR, chromatin 
      immunoprecipitation and promoter assays. KEY RESULTS: Inhibition of MMP-9 
      expression by inhibitors of Src (PP1), platelet-derived growth factor (PDGF) 
      receptor and epithelial growth factor (EGF) receptor or transfection with siRNA 
      for Src and Akt prevented IL-1beta-induced migration of A549 cells. These 
      tyrosine kinases were involved through phosphorylation of Src, PDGF, or EGF 
      receptors (EGFRs) via the formation of Src/PDGFR or Src/EGFR complexes, 
      attenuated by PP1. IL-1beta-induced MMP-9 expression through EGFR transactivation 
      was diminished by inhibitors of MMPs and heparin-binding EGF-like factor 
      (HB-EGF), or a neutralizing HB-EGF antibody. IL-1beta-stimulated activation and 
      translocation of Akt and NF-kappaB (p65); the recruitment of activated NF-kappaB 
      (p65) to the MMP-9 promoter region was attenuated by LY294002. CONCLUSIONS AND 
      IMPLICATIONS: IL-1beta-induced MMP-9 expression and cell migration was mediated 
      through c-Src-dependent transactivation of EGFR/PDGFR/PI3K/Akt linking to the 
      NF-kappaB pathway in A549 cells.
FAU - Cheng, Ching-Yi
AU  - Cheng CY
AD  - Department of Pharmacology, Chang Gung University, Tao-Yuan, Taiwan.
FAU - Kuo, Chang-Ting
AU  - Kuo CT
FAU - Lin, Chih-Chung
AU  - Lin CC
FAU - Hsieh, Hsi-Lung
AU  - Hsieh HL
FAU - Yang, Chuen-Mao
AU  - Yang CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Transcription Factor RelA)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Blotting, Western
MH  - Cell Culture Techniques
MH  - Cell Line, Tumor
MH  - Cell Movement/*drug effects
MH  - Chromatin Immunoprecipitation
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Genes, src/*physiology
MH  - Humans
MH  - Interleukin-1beta/*pharmacology/physiology
MH  - Luciferases/genetics
MH  - Lung Neoplasms/enzymology/immunology/pathology
MH  - Matrix Metalloproteinase 9/*biosynthesis/genetics/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Growth Factor/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Transcription Factor RelA/genetics/metabolism
MH  - Transcriptional Activation/*drug effects
PMC - PMC2936833
EDAT- 2010/07/24 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/08/01
CRDT- 2010/07/24 06:00
PHST- 2010/07/24 06:00 [entrez]
PHST- 2010/07/24 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/08/01 00:00 [pmc-release]
AID - BPH858 [pii]
AID - 10.1111/j.1476-5381.2010.00858.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2010 Aug;160(7):1595-610. doi: 10.1111/j.1476-5381.2010.00858.x.