PMID- 17460254
OWN - NLM
STAT- MEDLINE
DCOM- 20070613
LR  - 20131121
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 48
IP  - 5
DP  - 2007 May
TI  - Mitomycin C upregulates IL-8 and MCP-1 chemokine expression via mitogen-activated 
      protein kinases in corneal fibroblasts.
PG  - 2009-16
AB  - PURPOSE: To investigate the expression of chemokines and their signaling pathways 
      after application of mitomycin C (MMC) to corneal fibroblasts. METHODS: Primary 
      porcine and human corneal fibroblasts from passages 3 to 6 were treated with MMC 
      at concentrations of 0.05, 0.1, or 0.2 mg/mL for 1, 2, 5, or 10 minutes. The 
      relative expression of interleukin-8 (IL-8) and monocyte chemoattractant 
      protein-1 (MCP-1) were investigated with reverse transcription, and quantitative 
      real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent 
      assay (ELISA). The effects of MMC on the activation of kinases were analyzed by 
      Western blot analysis with specific antiphosphokinase antibodies. The signaling 
      pathways by which MMC regulates the expression of IL-8 and MCP-1 were evaluated 
      by pharmacological kinase-specific inhibitors. RESULTS: The expression of IL-8 
      and MCP-1 were upregulated after MMC treatment in a time- and 
      concentration-dependent manner. Furthermore, the upregulated expression of IL-8 
      and MCP-1 increased with longer incubation time. MMC treatment enhanced the 
      phosphorylation of p38, JNK, and ERK at different time points. The MMC-related 
      IL-8 and MCP-1 expression was inhibited by both a p38 inhibitor (SB203580) and an 
      ERK inhibitor (PD98059). A JNK inhibitor (SP600125) reduced the expression of 
      MMC-induced MCP-1 but not of IL-8. CONCLUSIONS: MMC treatment upregulated the 
      expression of IL-8 and MCP-1 mRNA and protein secretion by the activation of 
      mitogen-activated protein kinases (MAPKs) in corneal fibroblasts.
FAU - Chou, San-Fang
AU  - Chou SF
AD  - Department of Ophthalmology, Far Eastern Memorial Hospital, Ban-Chiao, Taipei, 
      Taiwan.
FAU - Chang, Shu-Wen
AU  - Chang SW
FAU - Chuang, Jia-Ling
AU  - Chuang JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Alkylating Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Interleukin-8)
RN  - 50SG953SK6 (Mitomycin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Alkylating Agents/*pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Corneal Stroma/cytology/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/drug effects/metabolism
MH  - Humans
MH  - Interleukin-8/*metabolism
MH  - MAP Kinase Kinase 4/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Mitomycin/*pharmacology
MH  - Phosphorylation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Swine
MH  - Time Factors
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
EDAT- 2007/04/27 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/04/27 09:00
PHST- 2007/04/27 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/04/27 09:00 [entrez]
AID - 48/5/2009 [pii]
AID - 10.1167/iovs.06-0835 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2007 May;48(5):2009-16. doi: 10.1167/iovs.06-0835.