The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal pigment epithelial cells - implication in subretinal immune privilege in the aging eye

Chang Luo, Jiawu Zhao, Mei Chen, Heping Xu

Research output: Contribution to journalArticle

4 Citations (Scopus)
224 Downloads (Pure)

Abstract

Age-related para-inflammation in the retina-choroidal interface is featured by low-levels of complement activation and subretinal macrophage accumulation. This study aimed to understand how complement expression in macrophages is regulated by retinal pigment epithelium (RPE). Bone marrow-derived macrophages (BMDMs) and RPE cells were cultured from 8-10 weeks old C57BL/6J mice. The BMDMs were co-cultured with normal RPE, or oxidized photoreceptor outer segment (oxPOS) or TNF-α pre-treated RPE, or apoptotic RPE, or RPE-choroid eyecups. Macrophages were then isolated and processed for real-time RT-PCR. The expression of complement inhibitor C1INH in BMDMs was significantly upregulated by RPE and RPE-choroid eyecups. The eyecups also upregulated CFH, CD59a, and Crry in BMDMs. oxPOS pre-treated RPE upregulated C1qb but down-regulated C3 expression in BMDMs. TNF-α pre-treated RPE enhanced C1INH and CFB expression. When BMDMs were treated with apoptotic RPE, the expression of C1qb, CFH, and CD59a was reduced, whereas the expression of C3, CFB and C1INH was increased. Our results suggest that RPE can modulate macrophages complement expression at the retina-choroidal interface even under aging or oxidative conditions. However, during inflammation, they may promote the alternative pathway of complement activation through down-regulating CFH and CD59a and upregulating CFB and C3.

Original languageEnglish
Pages (from-to)1380-1389
Number of pages10
JournalAging
Volume10
Issue number6
Early online date13 Jun 2018
DOIs
Publication statusPublished - 13 Jun 2018

Keywords

  • Aging
  • Complement
  • Macrophages
  • Retinal pigment epithelial cells
  • Subretinal immune privilege

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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