RGD Reference Report - Caveolin-1 increases proinflammatory chemoattractants and blood-retinal barrier breakdown but decreases leukocyte recruitment in inflammation. - Rat Genome Database

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Caveolin-1 increases proinflammatory chemoattractants and blood-retinal barrier breakdown but decreases leukocyte recruitment in inflammation.

Authors: Li, X  Gu, X  Boyce, TM  Zheng, M  Reagan, AM  Qi, H  Mandal, N  Cohen, AW  Callegan, MC  Carr, DJ  Elliott, MH 
Citation: Li X, etal., Invest Ophthalmol Vis Sci. 2014 Aug 26;55(10):6224-34. doi: 10.1167/iovs.14-14613.
RGD ID: 11528560
Pubmed: PMID:25159208   (View Abstract at PubMed)
PMCID: PMC4183075   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.14-14613   (Journal Full-text)

PURPOSE: Caveolin-1 (Cav-1), the signature protein of caveolae, modulates inflammatory responses, and innate immunity. However, Cav-1's role in retinal inflammation has not been rigorously tested. In this study, we examined the effect of Cav-1 ablation on the sensitivity of the retina to inflammation. METHODS: Cav-1 knockout (KO) mice were challenged by intravitreal injection of lipopolysaccharide (LPS) and inflammatory cell recruitment was assessed by flow cytometry and immunohistochemistry. Leukostasis was assessed in retinal flatmounts after perfusion with FITC-labeled Concanavalin A (FITC-ConA). Chemoattractants were measured by multiplex immunoassays. Blood-retinal barrier (BRB) breakdown was assessed quantitatively by a FITC-dextran permeability assay. The ratio of extravascular to total immune cells was determined by CD45 immunohistochemistry of retinal flatmounts. RESULTS: Inflammatory challenge resulted in significant blunting of proinflammatory cytokine (monocyte chemoattractant protein-1 [MCP-1/CCL2], CXCL1/KC, IL-6, and IL-1beta) responses as well as reduced inflammatory BRB breakdown in Cav-1 KO retinas. Paradoxically, Cav-1 deficiency resulted in significantly increased recruitment of immune cells compared with controls as well as increased leukostasis. A similar ratio of extravascular/total leukocytes were found in Cav-1 KO and wild-type (WT) retinas suggesting that Cav-1 deficient leukocytes were as competent to extravasate as those from WT mice. We found increased levels of circulating immune cells in naive (not challenged with LPS) Cav-1 KO mice compared with controls. CONCLUSIONS: Caveolin-1 paradoxically modulates inflammatory signaling and leukocyte infiltration through distinct mechanisms. We hypothesize that Cav-1 expression may enhance inflammatory signaling while at the same time supporting the physical properties of the BRB.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinitis  ISOCcl2 (Mus musculus)11528560; 11528560protein:increased expression:retina (mouse)RGD 
retinitis  IEP 11528560protein:increased expression:retina (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)


Additional Information