PMID- 16186362
OWN - NLM
STAT- MEDLINE
DCOM- 20051121
LR  - 20161124
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 46
IP  - 10
DP  - 2005 Oct
TI  - JNK regulates MCP-1 expression in adenovirus type 19-infected human corneal 
      fibroblasts.
PG  - 3777-82
AB  - PURPOSE: Previous studies indicate that adenovirus type 19 (Ad19) infection of 
      human corneal fibroblasts (HCFs) induces the expression of several 
      proinflammatory mediators, including IL-8 and monocyte chemoattractant protein-1 
      (MCP-1), and that the tyrosine kinase c-Src and its downstream target, the 
      mitogen-activated protein kinase ERK1/2, mediate IL-8 expression. In this 
      context, the authors sought to investigate the potential role of another 
      mitogen-activated protein kinase, c-Jun N-terminal kinase (JNK), in adenoviral 
      ocular pathogenesis. METHODS: Ad19- and mock-infected HCFs were solubilized at 
      various time points after infection, and cell lysates were subjected to SDS-PAGE 
      followed by immunoblot analysis with a panel of antibodies against components of 
      the MKK7/JNK/c-Jun pathway or immunoprecipitated for JNK assay. The induction of 
      chemokine mRNA and protein was determined by real-time PCR and ELISA, 
      respectively. RESULTS: Ad19 induced the phosphorylation of MKK7, JNK, and the 
      downstream transcription factor c-Jun in HCFs at 15 and 30 minutes after 
      infection. JNK activity was demonstrated at 30 minutes after infection using the 
      GST-c-Jun fusion protein as a target substrate. SP600125, a specific 
      pharmacologic inhibitor of JNK, blocked MCP-1 but not IL-8 mRNA and protein 
      expression. Finally, PP2, a specific inhibitor of c-Src previously shown to 
      inhibit the expression of both IL-8 and MCP-1 in Ad19-infected HCFs, also blocked 
      JNK phosphorylation after infection. CONCLUSIONS: The MKK7/JNK/c-Jun cascade is 
      rapidly activated and mediates MCP-1 expression in Ad19-infected HCFs. 
      Furthermore, the activation of c-Src on Ad19 infection appears to regulate both 
      the ERK and the JNK pathways.
FAU - Xiao, Jingnan
AU  - Xiao J
AD  - Department of Ophthalmology, University of Oklahoma Health Sciences Center, 
      73104, USA.
FAU - Chodosh, James
AU  - Chodosh J
LA  - eng
GR  - P30 EY12190/EY/NEI NIH HHS/United States
GR  - R01 EY13124/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 7)
RN  - EC 2.7.12.2 (MAP2K7 protein, human)
SB  - IM
MH  - Adenoviruses, Human/*physiology
MH  - Cell Culture Techniques
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Cornea/*metabolism/*virology
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/metabolism/virology
MH  - Gene Expression
MH  - Humans
MH  - Immunoblotting
MH  - JNK Mitogen-Activated Protein Kinases/*physiology
MH  - MAP Kinase Kinase 7/metabolism
MH  - Phosphorylation
MH  - Polymerase Chain Reaction
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/*physiology
EDAT- 2005/09/28 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/09/28 09:00
PHST- 2005/09/28 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/09/28 09:00 [entrez]
AID - 46/10/3777 [pii]
AID - 10.1167/iovs.05-0724 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3777-82. doi: 10.1167/iovs.05-0724.