Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells

Matthew D. Silverman, David O. Zamora, Yuzhen Pan, Paul V. Texeira, Seung Hee Baek, Stephen Planck, James (Jim) Rosenbaum

Research output: Contribution to journalArticle

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Abstract

PURPOSE. Fractalkine (FKN) is a dual-adhesion molecule-chemokine that plays a role in inflammation but has not been explored in the eye. In the current study, constitutive expression of FKN was identified in human iris and retina, and its regulation by various cytokines in endothelial cells (ECs) and stromal cells from human iris, retina, and choroid was investigated. METHODS. Human iris and retina explants were evaluated for FKN mRNA and protein expression using RT-PCR and immunohistochemistry, respectively. Cultured ocular ECs and stromal cells were stimulated with various inflammatory mediators (endotoxin; TNFα; interferon-γ; interleukin (IL)-1α, -4, -10, -13, -17, and -18; and/or CD40 ligand, or combinations thereof), with FKN mRNA being subsequently evaluated by cDNA array and/or RT-PCR and FKN protein by enzyme-linked immunoculture assay (ELICA) and/or by Western blot analysis. RESULTS. Iris and retina explants constitutively expressed FKN protein in microvascular ECs and also in several stromal cell types. Iris and retina both express FKN mRNA. TNFa upregulated FKN in iris explants. All ocular microvascular ECs and stromal cultures expressed low FKN mRNA and/or protein levels, which were variably upregulated by endotoxin, TNFα, interferon-γ, IL-1α, and/or CD40 ligand, but not by IL-18. In ECs, the Th2 cytokines IL-4 and -13, but not IL-10, reduced TNFα-induced FKN protein. IL-17, usually considered proinflammatory, reduced TNFα-induced FKN protein in ocular ECs. CONCLUSIONS. FKN is expressed in various ocular tissues and cells. Inflammatory mediator modulation of ocular FKN expression suggests that this adhesive chemokine may play important roles in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis.

Original languageEnglish (US)
Pages (from-to)1608-1615
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number4
DOIs
StatePublished - Apr 1 2003

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Chemokine CX3CL1
Cultured Cells
Iris
Endothelial Cells
Retina
Stromal Cells
Messenger RNA
CD40 Ligand
Proteins
Interleukin-1
Chemokines
Endotoxins
Interleukin-4
Interferons
Cytokines
Anterior Uveitis
Polymerase Chain Reaction
Interleukin-18
Interleukin-13
Choroid

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells. / Silverman, Matthew D.; Zamora, David O.; Pan, Yuzhen; Texeira, Paul V.; Baek, Seung Hee; Planck, Stephen; Rosenbaum, James (Jim).

In: Investigative Ophthalmology and Visual Science, Vol. 44, No. 4, 01.04.2003, p. 1608-1615.

Research output: Contribution to journalArticle

Silverman, Matthew D. ; Zamora, David O. ; Pan, Yuzhen ; Texeira, Paul V. ; Baek, Seung Hee ; Planck, Stephen ; Rosenbaum, James (Jim). / Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells. In: Investigative Ophthalmology and Visual Science. 2003 ; Vol. 44, No. 4. pp. 1608-1615.
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abstract = "PURPOSE. Fractalkine (FKN) is a dual-adhesion molecule-chemokine that plays a role in inflammation but has not been explored in the eye. In the current study, constitutive expression of FKN was identified in human iris and retina, and its regulation by various cytokines in endothelial cells (ECs) and stromal cells from human iris, retina, and choroid was investigated. METHODS. Human iris and retina explants were evaluated for FKN mRNA and protein expression using RT-PCR and immunohistochemistry, respectively. Cultured ocular ECs and stromal cells were stimulated with various inflammatory mediators (endotoxin; TNFα; interferon-γ; interleukin (IL)-1α, -4, -10, -13, -17, and -18; and/or CD40 ligand, or combinations thereof), with FKN mRNA being subsequently evaluated by cDNA array and/or RT-PCR and FKN protein by enzyme-linked immunoculture assay (ELICA) and/or by Western blot analysis. RESULTS. Iris and retina explants constitutively expressed FKN protein in microvascular ECs and also in several stromal cell types. Iris and retina both express FKN mRNA. TNFa upregulated FKN in iris explants. All ocular microvascular ECs and stromal cultures expressed low FKN mRNA and/or protein levels, which were variably upregulated by endotoxin, TNFα, interferon-γ, IL-1α, and/or CD40 ligand, but not by IL-18. In ECs, the Th2 cytokines IL-4 and -13, but not IL-10, reduced TNFα-induced FKN protein. IL-17, usually considered proinflammatory, reduced TNFα-induced FKN protein in ocular ECs. CONCLUSIONS. FKN is expressed in various ocular tissues and cells. Inflammatory mediator modulation of ocular FKN expression suggests that this adhesive chemokine may play important roles in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis.",
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T1 - Constitutive and inflammatory mediator-regulated fractalkine expression in human ocular tissues and cultured cells

AU - Silverman, Matthew D.

AU - Zamora, David O.

AU - Pan, Yuzhen

AU - Texeira, Paul V.

AU - Baek, Seung Hee

AU - Planck, Stephen

AU - Rosenbaum, James (Jim)

PY - 2003/4/1

Y1 - 2003/4/1

N2 - PURPOSE. Fractalkine (FKN) is a dual-adhesion molecule-chemokine that plays a role in inflammation but has not been explored in the eye. In the current study, constitutive expression of FKN was identified in human iris and retina, and its regulation by various cytokines in endothelial cells (ECs) and stromal cells from human iris, retina, and choroid was investigated. METHODS. Human iris and retina explants were evaluated for FKN mRNA and protein expression using RT-PCR and immunohistochemistry, respectively. Cultured ocular ECs and stromal cells were stimulated with various inflammatory mediators (endotoxin; TNFα; interferon-γ; interleukin (IL)-1α, -4, -10, -13, -17, and -18; and/or CD40 ligand, or combinations thereof), with FKN mRNA being subsequently evaluated by cDNA array and/or RT-PCR and FKN protein by enzyme-linked immunoculture assay (ELICA) and/or by Western blot analysis. RESULTS. Iris and retina explants constitutively expressed FKN protein in microvascular ECs and also in several stromal cell types. Iris and retina both express FKN mRNA. TNFa upregulated FKN in iris explants. All ocular microvascular ECs and stromal cultures expressed low FKN mRNA and/or protein levels, which were variably upregulated by endotoxin, TNFα, interferon-γ, IL-1α, and/or CD40 ligand, but not by IL-18. In ECs, the Th2 cytokines IL-4 and -13, but not IL-10, reduced TNFα-induced FKN protein. IL-17, usually considered proinflammatory, reduced TNFα-induced FKN protein in ocular ECs. CONCLUSIONS. FKN is expressed in various ocular tissues and cells. Inflammatory mediator modulation of ocular FKN expression suggests that this adhesive chemokine may play important roles in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis.

AB - PURPOSE. Fractalkine (FKN) is a dual-adhesion molecule-chemokine that plays a role in inflammation but has not been explored in the eye. In the current study, constitutive expression of FKN was identified in human iris and retina, and its regulation by various cytokines in endothelial cells (ECs) and stromal cells from human iris, retina, and choroid was investigated. METHODS. Human iris and retina explants were evaluated for FKN mRNA and protein expression using RT-PCR and immunohistochemistry, respectively. Cultured ocular ECs and stromal cells were stimulated with various inflammatory mediators (endotoxin; TNFα; interferon-γ; interleukin (IL)-1α, -4, -10, -13, -17, and -18; and/or CD40 ligand, or combinations thereof), with FKN mRNA being subsequently evaluated by cDNA array and/or RT-PCR and FKN protein by enzyme-linked immunoculture assay (ELICA) and/or by Western blot analysis. RESULTS. Iris and retina explants constitutively expressed FKN protein in microvascular ECs and also in several stromal cell types. Iris and retina both express FKN mRNA. TNFa upregulated FKN in iris explants. All ocular microvascular ECs and stromal cultures expressed low FKN mRNA and/or protein levels, which were variably upregulated by endotoxin, TNFα, interferon-γ, IL-1α, and/or CD40 ligand, but not by IL-18. In ECs, the Th2 cytokines IL-4 and -13, but not IL-10, reduced TNFα-induced FKN protein. IL-17, usually considered proinflammatory, reduced TNFα-induced FKN protein in ocular ECs. CONCLUSIONS. FKN is expressed in various ocular tissues and cells. Inflammatory mediator modulation of ocular FKN expression suggests that this adhesive chemokine may play important roles in regulating leukocyte efflux in inflammatory eye diseases, such as anterior uveitis and retinochoroiditis.

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