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

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)e45801
Number of pages9
JournalPloS ONE
Volume7
Issue number9
Early online date20 Sep 2012
DOIs
Publication statusPublished - 20 Sep 2012

Fingerprint

Interleukin-27
Complement Factor H
interleukins
retina
Retina
complement
Interferon Regulatory Factor-1
Macular Degeneration
Up-Regulation
Complement Activation
Blindness
Ganglia
blindness
Anti-Inflammatory Agents
Epithelial Cells
Chemical activation
Cells
Cytokines
etiology
Inflammation

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

Cite this

Amadi-Obi, A., Yu, C-R., Dambuza, I., Kim, S-H., Marrero, B., & Egwuagu, C. E. (2012). Interleukin 27 induces the expression of complement factor H (CFH) in the retina. PloS ONE, 7(9), e45801. https://doi.org/10.1371/journal.pone.0045801

Interleukin 27 induces the expression of complement factor H (CFH) in the retina. / Amadi-Obi, Ahjoku; Yu, Cheng-Rong; Dambuza, Ivy; Kim, Sung-Hye; Marrero, Bernadette; Egwuagu, Charles E.

In: PloS ONE, Vol. 7, No. 9, 20.09.2012, p. e45801.

Research output: Contribution to journalArticle

Amadi-Obi, A, Yu, C-R, Dambuza, I, Kim, S-H, Marrero, B & Egwuagu, CE 2012, 'Interleukin 27 induces the expression of complement factor H (CFH) in the retina' PloS ONE, vol. 7, no. 9, pp. e45801. https://doi.org/10.1371/journal.pone.0045801
Amadi-Obi A, Yu C-R, Dambuza I, Kim S-H, Marrero B, Egwuagu CE. Interleukin 27 induces the expression of complement factor H (CFH) in the retina. PloS ONE. 2012 Sep 20;7(9):e45801. https://doi.org/10.1371/journal.pone.0045801
Amadi-Obi, Ahjoku ; Yu, Cheng-Rong ; Dambuza, Ivy ; Kim, Sung-Hye ; Marrero, Bernadette ; Egwuagu, Charles E. / Interleukin 27 induces the expression of complement factor H (CFH) in the retina. In: PloS ONE. 2012 ; Vol. 7, No. 9. pp. e45801.
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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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AU - Dambuza, Ivy

AU - Kim, Sung-Hye

AU - Marrero, Bernadette

AU - Egwuagu, Charles E

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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.

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