TNFalpha suppression of corneal epithelium migration.
OBJECTIVE
To evaluate the role of tumor necrosis factor alpha (TNFalpha) in regulation of corneal epithelial cell migration.


METHODS
Cell culture of immortalized corneal epithelial cell line was employed to examine the role of transforming growth factor beta1 (TGFbeta1) and TNFalpha on cell migration and cell signaling. Healing of central epithelial defect was also observed in organ culture in the presence or absence of neutralizing antibody against either TNFalpha or TGFbeta1.


RESULTS
In cell cultures of corneal epithelial cell line, adding TNFalpha suppresses activation of p38 signal and cell migration, but not Smad2 activation, upon TGFbeta1 exposure. In an organ culture system, healing of an epithelial defect was promoted by the loss of TNFalpha. A neutralizing antibody against TNFalpha also promoted closure of an epithelial defect of organ cultured WT mouse corneas. Anti-TGFbeta neutralizing antibody reversed facilitation of epithelial healing in KO corneas in organ culture.


CONCLUSIONS
TNFalpha inhibits migration of corneal epithelial cells.
Okada
Yuka
Y
Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan.
Ikeda
Kazuo
K
Yamanaka
Osamu
O
Miyamoto
Takeshi
T
Kitano
Ai
A
Kao
Winston W-Y
WW
Saika
Shizuya
S
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D003646:Debridement; D019573:Epithelium, Corneal / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases