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Cited by 77Ocular Diseases and Behçet’s SyndromeChemokine receptors and signalingRetinal Diseases and Treatments

Control of chemokine production at the blood-retina barrier

Open access
Crane, I. J., Wallace, C. A., Mckillop‐Smith, S., Forrester, J. V.·2000·Immunology
DOI 10.1046/j.0019-2805.2000.01105.xPMC PMC2327097
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Abstract

Summary: Chemokine production at the blood–retina barrier probably plays a critical role in determining the influx of tissue‐damaging cells from the circulation into the retina during inflammation. The blood–retina barrier comprises the retinal microvascular endothelium and the retinal pigment epithelium. Chemokine expression and production by human retinal microvascular endothelial cells (REC) have never been reported previously, so we examined the in vitro expression and production of monocyte chemoattractant protein‐1 (MCP‐1), regulated on activation of normal T‐cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)‐1α, MIP‐1β, interleukin (IL)‐8, epithelial cell‐derived neutrophil activating protein‐78 (ENA‐78) and growth related oncogene α (GROα) in these cells, both unstimulated and stimulated by cytokines likely to be present during the evolution of an inflammatory response. We compared this to expression and production of these chemokines in vitro in human retinal pigment epithelial cells (RPE). MCP‐1 was expressed and produced constitutively by REC but all the chemokines were produced in greater amounts upon stimulation with the proinflammatory cytokines IL‐1β and tumour necrosis factor‐α (TNF‐α). MCP‐1 and IL‐8 were produced at much higher levels than the other chemokines tested. MIP‐1α and MIP‐1β were present only at low levels, even after stimulation with IL‐1β and TNF‐α. Cytokines with greater anti‐inflammatory activity, such as IL‐4, IL‐10, IL‐13, transforming growth factor‐β (TGF‐β) and IL‐6, had little effect on chemokine production either by REC alone or after stimulation with IL‐1β and TNF‐α. RPE, although a very different cell type, showed a similar pattern of expression and production of chemokines, indicating the site‐specific nature of chemokine production. Chemokine production by REC and RPE is probably significant in selective leucocyte recruitment during the development of inflammation in the retina.

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  • Retinal inflammation can induce local expression of pro-inflammatory cytokines and chemokines and upregulate adhesion molecules on the basal RPE membrane, leading to leukocyte recruitment and breakdown of the blood-retinal barrier.

    “However, retinal inflammation can induce local expression of pro-inflammatory cytokines and chemokines and can upregulate adhesion molecules on the basal RPE membrane, which leads to the recruitment of leukocytes and breakdown of the blood-retinal barrier.10,11”

    From Characterizing the cellular immune response to subretinal AAV gene therapy in the murine retina (2021) · cites this paper as [10]

    The Abstract and Discussion report that pro-inflammatory cytokines increase chemokine production by retinal endothelial and pigment epithelial cells, and link chemokines to leukocyte recruitment. The Introduction describes blood–retinal barrier breakdown during inflammatory eye disease. The paper does not support the claimed upregulation of adhesion molecules on the basal RPE membrane or establish that this mechanism causes barrier breakdown. (LLM, conf=0.86)

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Research works printed but not linked: 2

  1. Rollins BJ. Chemokines. Blood 1997; 90:909±28.
  2. Forrester JV, Lumsden L, Liversidge J, Kuppner M, Mesri M. Immunoregulation of uveoretinal in¯ammation. Prog Retinal Eye Res 1995; 14:393±412.

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Related

Authors
Crane, I. J., Wallace, C. A., Mckillop‐Smith, S., & Forrester, J. V.
Affiliations
University of Aberdeen (GB)
Corresponding author
Crane, I. J.
ORCID
Venue
Immunology
Publisher
Wiley
Published
2000-11
Volume
101
Issue
3
Pages
426-433
ISSN
  • 0019-2805 (ISSN-L)
  • 1365-2567
DOI
10.1046/j.0019-2805.2000.01105.x
PMC
PMC2327097
OpenAlex
W2008325701
Cited by
77
References
42
Citations by year
2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 2 · 2013: 1 · 2012: 7
FWCI
4.18
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2899 d)
Locations
  • Immunology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
chemokines, blood-retinal barrier, retinal microvascular endothelial cells, retinal pigment epithelium, MCP-1, RANTES, MIP-1α, MIP-1β, interleukin-8, CXCL5, CXCL1, cytokine induction, IL-1β, TNF-α, retinal inflammation, leukocyte recruitment, chemokine expression
MeSH terms
Blood-Retinal Barrier, Endothelium, Vascular, Humans, Pigment Epithelium of Eye, RNA, Messenger, Gene Expression, Chemokines, Cell Culture Techniques, Chemokine CCL2, Chemokine CCL5, Reverse Transcriptase Polymerase Chain Reaction

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