Upregulation of tumor necrosis factor receptor 1 and TNF-alpha converting enzyme during corneal wound healing.
OBJECTIVE
To elucidate tumor necrosis factor (TNF) receptor-1 (TNFR1) and TNF-alpha converting enzyme (TACE) involvement during corneal wound healing.


METHODS
The corneas of BALB/c mice cornea were scarred by alkali burns using filter paper dipped in 1N NaOH solution. TACE and TNFR1 expression in the alkali-burned corneas were evaluated by immunohistochemistry (total, 16 eyes). Using cultured fibroblasts (human) and macrophages (mice), we evaluated the release of soluble TNF-alpha (sTNF-alpha) and soluble TNFR1 (sTNFR1) in the supernatant by enzyme-linked immunosorbent assay after stimulating TACE activity with phorbol myristate acetate (PMA).


RESULTS
In alkali-burned corneas, both TACE and TNFR1 expression were observed in the stromal cells after the acute phase of wound healing response. In macrophage-cultured supernatant, both sTNF-alpha and sTNFR1 release were promoted by PMA stimulation. On the other hand, only sTNFR1 released by PMA stimulation was observed in fibroblast-cultured supernatant.


CONCLUSIONS
TACE and TNFR1 were expressed mainly after the acute phase of corneal wound healing. The TACE-dependent extracellular release of sTNFR1 was recognized in cultured fibroblasts and macrophages.
Sakimoto
Tohru
T
Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan. torusaki@med.nihon-u.ac.jp.|Department of Ophthalmology, Nihon University School of Medicine, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan. torusaki@med.nihon-u.ac.jp.
Yamada
Ai
A
Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.
Kanno
Hitoshi
H
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
Sawa
Mitsuru
M
Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D002057:Burns, Chemical / Q000378:metabolism*; D002478:Cells, Cultured; D003315:Cornea / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005126:Eye Burns / Q000139:chemically induced*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D012972:Sodium Hydroxide; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D012972:Sodium Hydroxide; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse; D013755:Tetradecanoylphorbol Acetate