Interleukin 27 induces the expression of complement factor H (CFH) in the retina

Ahjoku Amadi-Obi; Cheng-Rong Yu; Ivy Dambuza; Sung-Hye Kim; Bernadette Marrero; Charles E Egwuagu

doi:10.1371/journal.pone.0045801

Interleukin 27 induces the expression of complement factor H (CFH) in the retina

Ahjoku Amadi-Obi, Cheng-Rong Yu, Ivy Dambuza, Sung-Hye Kim, Bernadette Marrero, Charles E Egwuagu

Applied Medicine

National Institutes of Health

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

Abstract

Complement factor H (CFH) is a central regulator of the complement system and has been implicated in the etiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. In view of previous studies showing that reduced expression of CFH in the retina is a risk factor for developing AMD, there is significant interest in understanding how CFH expression is regulated in the retina. In this study, we have shown that the anti-inflammatory cytokine, IL-27, induced CFH expression in mouse retinal cells and human retinal pigmented epithelial cells (RPE) through STAT1-mediated up-regulation of Interferon Regulatory Factor-1 (IRF-1) and IRF-8. We further show that cells in the ganglion and inner-nuclear layers of the retina constitutively express IRF-1 and IRF-8 and enhanced CFH expression in the retina during ocular inflammation correlated with significant increase in the expression of IRF-1, IRF-8 and IL-27 (IL-27p28 and Ebi3). Our data thus reveal a novel role of IL-27 in regulating complement activation through up-regulation of CFH and suggest that defects in IL-27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD.

Original language	English
Pages (from-to)	e45801
Number of pages	9
Journal	PloS ONE
Volume	7
Issue number	9
Early online date	20 Sept 2012
DOIs	https://doi.org/10.1371/journal.pone.0045801
Publication status	Published - 20 Sept 2012

Bibliographical note

Acknowledgements
We thank Dr. Li Zhang (NEI, National Institutes of Health) for critical reading of the manuscript.

Keywords

Animals
Cells, Cultured
Complement Factor H/genetics
Gene Expression
Humans
Interferon Regulatory Factor-1/genetics
Interferon Regulatory Factors/genetics
Interleukins/genetics
Macular Degeneration/metabolism
Mice
Mice, Inbred C57BL
Papilledema/metabolism
Primary Cell Culture
Retina/metabolism
Retinal Ganglion Cells/metabolism
Retinal Photoreceptor Cell Inner Segment/metabolism
Retinal Vasculitis/metabolism
STAT1 Transcription Factor/metabolism
Transcriptional Activation
Uveitis/metabolism

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10.1371/journal.pone.0045801Licence: CC0

Interleukin 27 Induces the Expression of Complement Factor H (CFH) in the Retina
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title = "Interleukin 27 induces the expression of complement factor H (CFH) in the retina",

abstract = "Complement factor H (CFH) is a central regulator of the complement system and has been implicated in the etiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. In view of previous studies showing that reduced expression of CFH in the retina is a risk factor for developing AMD, there is significant interest in understanding how CFH expression is regulated in the retina. In this study, we have shown that the anti-inflammatory cytokine, IL-27, induced CFH expression in mouse retinal cells and human retinal pigmented epithelial cells (RPE) through STAT1-mediated up-regulation of Interferon Regulatory Factor-1 (IRF-1) and IRF-8. We further show that cells in the ganglion and inner-nuclear layers of the retina constitutively express IRF-1 and IRF-8 and enhanced CFH expression in the retina during ocular inflammation correlated with significant increase in the expression of IRF-1, IRF-8 and IL-27 (IL-27p28 and Ebi3). Our data thus reveal a novel role of IL-27 in regulating complement activation through up-regulation of CFH and suggest that defects in IL-27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD.",

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author = "Ahjoku Amadi-Obi and Cheng-Rong Yu and Ivy Dambuza and Sung-Hye Kim and Bernadette Marrero and Egwuagu, {Charles E}",

note = "Acknowledgements We thank Dr. Li Zhang (NEI, National Institutes of Health) for critical reading of the manuscript.",

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T1 - Interleukin 27 induces the expression of complement factor H (CFH) in the retina

AU - Amadi-Obi, Ahjoku

AU - Yu, Cheng-Rong

AU - Dambuza, Ivy

AU - Kim, Sung-Hye

AU - Marrero, Bernadette

AU - Egwuagu, Charles E

N1 - Acknowledgements We thank Dr. Li Zhang (NEI, National Institutes of Health) for critical reading of the manuscript.

PY - 2012/9/20

Y1 - 2012/9/20

N2 - Complement factor H (CFH) is a central regulator of the complement system and has been implicated in the etiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. In view of previous studies showing that reduced expression of CFH in the retina is a risk factor for developing AMD, there is significant interest in understanding how CFH expression is regulated in the retina. In this study, we have shown that the anti-inflammatory cytokine, IL-27, induced CFH expression in mouse retinal cells and human retinal pigmented epithelial cells (RPE) through STAT1-mediated up-regulation of Interferon Regulatory Factor-1 (IRF-1) and IRF-8. We further show that cells in the ganglion and inner-nuclear layers of the retina constitutively express IRF-1 and IRF-8 and enhanced CFH expression in the retina during ocular inflammation correlated with significant increase in the expression of IRF-1, IRF-8 and IL-27 (IL-27p28 and Ebi3). Our data thus reveal a novel role of IL-27 in regulating complement activation through up-regulation of CFH and suggest that defects in IL-27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD.

AB - Complement factor H (CFH) is a central regulator of the complement system and has been implicated in the etiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. In view of previous studies showing that reduced expression of CFH in the retina is a risk factor for developing AMD, there is significant interest in understanding how CFH expression is regulated in the retina. In this study, we have shown that the anti-inflammatory cytokine, IL-27, induced CFH expression in mouse retinal cells and human retinal pigmented epithelial cells (RPE) through STAT1-mediated up-regulation of Interferon Regulatory Factor-1 (IRF-1) and IRF-8. We further show that cells in the ganglion and inner-nuclear layers of the retina constitutively express IRF-1 and IRF-8 and enhanced CFH expression in the retina during ocular inflammation correlated with significant increase in the expression of IRF-1, IRF-8 and IL-27 (IL-27p28 and Ebi3). Our data thus reveal a novel role of IL-27 in regulating complement activation through up-regulation of CFH and suggest that defects in IL-27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD.

KW - Animals

KW - Cells, Cultured

KW - Complement Factor H/genetics

KW - Gene Expression

KW - Humans

KW - Interferon Regulatory Factor-1/genetics

KW - Interferon Regulatory Factors/genetics

KW - Interleukins/genetics

KW - Macular Degeneration/metabolism

KW - Mice

KW - Mice, Inbred C57BL

KW - Papilledema/metabolism

KW - Primary Cell Culture

KW - Retina/metabolism

KW - Retinal Ganglion Cells/metabolism

KW - Retinal Photoreceptor Cell Inner Segment/metabolism

KW - Retinal Vasculitis/metabolism

KW - STAT1 Transcription Factor/metabolism

KW - Transcriptional Activation

KW - Uveitis/metabolism

U2 - 10.1371/journal.pone.0045801

DO - 10.1371/journal.pone.0045801

M3 - Article

C2 - 23029250

SN - 1932-6203

VL - 7

SP - e45801

JO - PloS ONE

JF - PloS ONE

IS - 9

ER -

Interleukin 27 induces the expression of complement factor H (CFH) in the retina

Abstract

Bibliographical note

Keywords

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