PMID- 29905533
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20190930
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 10
IP  - 6
DP  - 2018 Jun 13
TI  - The expression of C1 inhibitor (C1INH) in macrophages is upregulated by retinal 
      pigment epithelial cells - implication in subretinal immune privilege in the 
      aging eye.
PG  - 1380-1389
LID - 10.18632/aging.101474 [doi]
AB  - 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-alpha 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-alpha 
      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.
FAU - Luo, Chang
AU  - Luo C
AD  - Centre for Experimental Medicine, School of Medicine, Dentistry & Biomedical 
      Science, Queen's University Belfast, Belfast, UK.
AD  - AIER Eye Institute, Changsha, China.
AD  - AIER School of Ophthalmology, Central South University, Changsha, China.
FAU - Zhao, Jiawu
AU  - Zhao J
AD  - Centre for Experimental Medicine, School of Medicine, Dentistry & Biomedical 
      Science, Queen's University Belfast, Belfast, UK.
FAU - Chen, Mei
AU  - Chen M
AD  - Centre for Experimental Medicine, School of Medicine, Dentistry & Biomedical 
      Science, Queen's University Belfast, Belfast, UK.
FAU - Xu, Heping
AU  - Xu H
AD  - Centre for Experimental Medicine, School of Medicine, Dentistry & Biomedical 
      Science, Queen's University Belfast, Belfast, UK.
AD  - AIER Eye Institute, Changsha, China.
AD  - AIER School of Ophthalmology, Central South University, Changsha, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Complement C1 Inhibitor Protein)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Complement C1 Inhibitor Protein/*metabolism
MH  - Epithelial Cells/*metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Photoreceptor Cells, Vertebrate/*radiation effects
MH  - Retinal Pigment Epithelium/*cytology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation
PMC - PMC6046230
OTO - NOTNLM
OT  - *aging
OT  - *complement
OT  - *macrophages
OT  - *retinal pigment epithelial cells
OT  - *subretinal immune privilege
COIS- CONFLICTS OF INTEREST: All authors disclose no commercial interests in any 
      subjects presented in this paper.
EDAT- 2018/06/16 06:00
MHDA- 2019/10/01 06:00
PMCR- 2018/06/01
CRDT- 2018/06/16 06:00
PHST- 2018/04/29 00:00 [received]
PHST- 2018/06/07 00:00 [accepted]
PHST- 2018/06/16 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/06/16 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - 101474 [pii]
AID - 10.18632/aging.101474 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2018 Jun 13;10(6):1380-1389. doi: 10.18632/aging.101474.