IL-4 induces eotaxin production in corneal keratocytes but not in epithelial cells

Kazumi Fukagawa, Toshiharu Nakajima, Hirohisa Saito, Kazuo Tsubota, Shigeto Shimmura, Michiya Natori, Koichi Hirai

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: In severe allergic eye diseases, the breakdown of epithelial barrier function can lead to severe corneal damage such as erosions or ulcers which often resist treatment. Although eosinophils are thought to play a crucial role in corneal tissue damage in severe ocular allergy, the mechanisms of eosinophil recruitment to the cornea has not been fully clarified. Eotaxin has been found in tears of severe allergic patients with corneal ulcer. In this study, we investigated whether the Th2 cytokine interleukin-4 (IL-4) induces eotaxin production in human corneal epithelial cells and keratocytes. Methods: Primary cultures of human corneal epithelial cells and keratocytes were incubated with IL-4 and/or TNF-α for 48 h. Released eotaxin was measured by ELISA, and the eotaxin proteins were visualized by immunocytochemistry. Eotaxin mRNA expression in cultured cells was analyzed by RT-PCR. Results: IL-4 induced eotaxin production in keratocytes in a dose- and time-dependent manner which was enhanced by TNF-α. There was no detectable eotaxin produced by corneal epithelial cells (< 5 pg/ml). The cytoplasm of keratocytes incubated with IL-4 stained positively against anti-eotaxin antibodies, while eotaxin mRNA was detected in keratocytes incubated with IL-4. Conclusions: Human corneal keratocytes, but not epithelial cells, are capable of producing eotaxin by stimulation with IL-4. Our results suggest that eotaxin production in keratocytes induced by IL-4 may play an important role in eosinophil recruitment to corneal ulcers in allergic ocular disease. Eotaxin production by keratocytes may explain the severity of allergic disease involving the corneal stroma. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)144-150
Number of pages7
JournalInternational Archives of Allergy and Immunology
Volume121
Issue number2
Publication statusPublished - 2000

Fingerprint

Corneal Keratocytes
Interleukin-4
Epithelial Cells
Eosinophils
Corneal Ulcer
Eye Diseases
Corneal Stroma
Messenger RNA
Tears
Cornea
Ulcer
Anti-Idiotypic Antibodies
Cultured Cells
Hypersensitivity
Cytoplasm
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Cytokines
Polymerase Chain Reaction

Keywords

  • Cornea
  • Eotaxin
  • IL-4
  • Keratoconjunctivitis, atopic
  • Keratoconjunctivitis, vernal

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IL-4 induces eotaxin production in corneal keratocytes but not in epithelial cells. / Fukagawa, Kazumi; Nakajima, Toshiharu; Saito, Hirohisa; Tsubota, Kazuo; Shimmura, Shigeto; Natori, Michiya; Hirai, Koichi.

In: International Archives of Allergy and Immunology, Vol. 121, No. 2, 2000, p. 144-150.

Research output: Contribution to journalArticle

Fukagawa, Kazumi ; Nakajima, Toshiharu ; Saito, Hirohisa ; Tsubota, Kazuo ; Shimmura, Shigeto ; Natori, Michiya ; Hirai, Koichi. / IL-4 induces eotaxin production in corneal keratocytes but not in epithelial cells. In: International Archives of Allergy and Immunology. 2000 ; Vol. 121, No. 2. pp. 144-150.
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abstract = "Background: In severe allergic eye diseases, the breakdown of epithelial barrier function can lead to severe corneal damage such as erosions or ulcers which often resist treatment. Although eosinophils are thought to play a crucial role in corneal tissue damage in severe ocular allergy, the mechanisms of eosinophil recruitment to the cornea has not been fully clarified. Eotaxin has been found in tears of severe allergic patients with corneal ulcer. In this study, we investigated whether the Th2 cytokine interleukin-4 (IL-4) induces eotaxin production in human corneal epithelial cells and keratocytes. Methods: Primary cultures of human corneal epithelial cells and keratocytes were incubated with IL-4 and/or TNF-α for 48 h. Released eotaxin was measured by ELISA, and the eotaxin proteins were visualized by immunocytochemistry. Eotaxin mRNA expression in cultured cells was analyzed by RT-PCR. Results: IL-4 induced eotaxin production in keratocytes in a dose- and time-dependent manner which was enhanced by TNF-α. There was no detectable eotaxin produced by corneal epithelial cells (< 5 pg/ml). The cytoplasm of keratocytes incubated with IL-4 stained positively against anti-eotaxin antibodies, while eotaxin mRNA was detected in keratocytes incubated with IL-4. Conclusions: Human corneal keratocytes, but not epithelial cells, are capable of producing eotaxin by stimulation with IL-4. Our results suggest that eotaxin production in keratocytes induced by IL-4 may play an important role in eosinophil recruitment to corneal ulcers in allergic ocular disease. Eotaxin production by keratocytes may explain the severity of allergic disease involving the corneal stroma. Copyright (C) 2000 S. Karger AG, Basel.",
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AU - Fukagawa, Kazumi

AU - Nakajima, Toshiharu

AU - Saito, Hirohisa

AU - Tsubota, Kazuo

AU - Shimmura, Shigeto

AU - Natori, Michiya

AU - Hirai, Koichi

PY - 2000

Y1 - 2000

N2 - Background: In severe allergic eye diseases, the breakdown of epithelial barrier function can lead to severe corneal damage such as erosions or ulcers which often resist treatment. Although eosinophils are thought to play a crucial role in corneal tissue damage in severe ocular allergy, the mechanisms of eosinophil recruitment to the cornea has not been fully clarified. Eotaxin has been found in tears of severe allergic patients with corneal ulcer. In this study, we investigated whether the Th2 cytokine interleukin-4 (IL-4) induces eotaxin production in human corneal epithelial cells and keratocytes. Methods: Primary cultures of human corneal epithelial cells and keratocytes were incubated with IL-4 and/or TNF-α for 48 h. Released eotaxin was measured by ELISA, and the eotaxin proteins were visualized by immunocytochemistry. Eotaxin mRNA expression in cultured cells was analyzed by RT-PCR. Results: IL-4 induced eotaxin production in keratocytes in a dose- and time-dependent manner which was enhanced by TNF-α. There was no detectable eotaxin produced by corneal epithelial cells (< 5 pg/ml). The cytoplasm of keratocytes incubated with IL-4 stained positively against anti-eotaxin antibodies, while eotaxin mRNA was detected in keratocytes incubated with IL-4. Conclusions: Human corneal keratocytes, but not epithelial cells, are capable of producing eotaxin by stimulation with IL-4. Our results suggest that eotaxin production in keratocytes induced by IL-4 may play an important role in eosinophil recruitment to corneal ulcers in allergic ocular disease. Eotaxin production by keratocytes may explain the severity of allergic disease involving the corneal stroma. Copyright (C) 2000 S. Karger AG, Basel.

AB - Background: In severe allergic eye diseases, the breakdown of epithelial barrier function can lead to severe corneal damage such as erosions or ulcers which often resist treatment. Although eosinophils are thought to play a crucial role in corneal tissue damage in severe ocular allergy, the mechanisms of eosinophil recruitment to the cornea has not been fully clarified. Eotaxin has been found in tears of severe allergic patients with corneal ulcer. In this study, we investigated whether the Th2 cytokine interleukin-4 (IL-4) induces eotaxin production in human corneal epithelial cells and keratocytes. Methods: Primary cultures of human corneal epithelial cells and keratocytes were incubated with IL-4 and/or TNF-α for 48 h. Released eotaxin was measured by ELISA, and the eotaxin proteins were visualized by immunocytochemistry. Eotaxin mRNA expression in cultured cells was analyzed by RT-PCR. Results: IL-4 induced eotaxin production in keratocytes in a dose- and time-dependent manner which was enhanced by TNF-α. There was no detectable eotaxin produced by corneal epithelial cells (< 5 pg/ml). The cytoplasm of keratocytes incubated with IL-4 stained positively against anti-eotaxin antibodies, while eotaxin mRNA was detected in keratocytes incubated with IL-4. Conclusions: Human corneal keratocytes, but not epithelial cells, are capable of producing eotaxin by stimulation with IL-4. Our results suggest that eotaxin production in keratocytes induced by IL-4 may play an important role in eosinophil recruitment to corneal ulcers in allergic ocular disease. Eotaxin production by keratocytes may explain the severity of allergic disease involving the corneal stroma. Copyright (C) 2000 S. Karger AG, Basel.

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KW - Keratoconjunctivitis, vernal

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