Role of IL-6 in angiotensin II-induced retinal vascular inflammation

Modesto Rojas, Wenbo Zhang, Dexter L. Lee, Maritza J. Romero, Doan T. Nguyen, Mohamed Al-Shabrawey, Nai Tse Tsai, Gregory I. Liou, Michael W. Brands, Robert W. Caldwell, Ruth B. Caldwell

Research output: Contribution to journalArticle

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Abstract

Purpose. The production of proinflammatory cytokines has been shown to play a critical role in a variety of retinal vascular diseases. Angiotensin II and VEGF have been implicated in the initiation of vascular inflammation and retinal vascular disease. However, detailed mechanisms of this process and interactions between inflammatory agonists and angiotensin II in promoting retinopathy are poorly understood. The present study was an investigation of the role of interleukin (IL)-6 in angiotensin II-induced retinopathy. Methods. Rats and IL-6-deficient and wild-type mice were treated with angiotensin II or IL-6, and their retinas were analyzed for leukocyte adhesion or for the expression and localization of VEGF or IL-6. Leukocyte adhesion was assayed by concanavalin A labeling. Vascular density was determined by morphometric analysis. NADPH oxidase activity was assayed by dihydroethidium imaging of superoxide. Results. Intravitreal injection of angiotensin II caused increases in IL-6 mRNA and protein and in leukocyte adhesion to the retinal vessels. IL-6 protein was localized to CD11b-positive microglia and macrophage-like cells. Angiotensin II treatment stimulated increases in retinal levels of VEGF expression and NADPH oxidase activity, which were associated with increased surface area and remodeling of the retinal vessels. These effects were blocked by knocking out IL-6. Intravitreal IL-6 directly induced leukocyte adhesion in both wild-type and IL-6-deficient mice. Conclusions. The results indicate that IL-6 expression is essential for angiotensin II-induced increases in retinal VEGF expression, leukostasis, and vascular remodeling. The data suggest a critical role for IL-6 in mediating angiotensin II-induced retinal vascular inflammation and remodeling.

Original languageEnglish (US)
Pages (from-to)1709-1718
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Retinal Vessels
Angiotensin II
Interleukin-6
Inflammation
Vascular Endothelial Growth Factor A
Leukocytes
Retinal Diseases
NADPH Oxidase
Vascular Diseases
Blood Vessels
Leukostasis
Intravitreal Injections
Microglia
Concanavalin A
Superoxides
Retina
Proteins
Macrophages
Cytokines

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Rojas, M., Zhang, W., Lee, D. L., Romero, M. J., Nguyen, D. T., Al-Shabrawey, M., ... Caldwell, R. B. (2010). Role of IL-6 in angiotensin II-induced retinal vascular inflammation. Investigative Ophthalmology and Visual Science, 51(3), 1709-1718. https://doi.org/10.1167/iovs.09-3375

Role of IL-6 in angiotensin II-induced retinal vascular inflammation. / Rojas, Modesto; Zhang, Wenbo; Lee, Dexter L.; Romero, Maritza J.; Nguyen, Doan T.; Al-Shabrawey, Mohamed; Tsai, Nai Tse; Liou, Gregory I.; Brands, Michael W.; Caldwell, Robert W.; Caldwell, Ruth B.

In: Investigative Ophthalmology and Visual Science, Vol. 51, No. 3, 03.2010, p. 1709-1718.

Research output: Contribution to journalArticle

Rojas, M, Zhang, W, Lee, DL, Romero, MJ, Nguyen, DT, Al-Shabrawey, M, Tsai, NT, Liou, GI, Brands, MW, Caldwell, RW & Caldwell, RB 2010, 'Role of IL-6 in angiotensin II-induced retinal vascular inflammation', Investigative Ophthalmology and Visual Science, vol. 51, no. 3, pp. 1709-1718. https://doi.org/10.1167/iovs.09-3375
Rojas, Modesto ; Zhang, Wenbo ; Lee, Dexter L. ; Romero, Maritza J. ; Nguyen, Doan T. ; Al-Shabrawey, Mohamed ; Tsai, Nai Tse ; Liou, Gregory I. ; Brands, Michael W. ; Caldwell, Robert W. ; Caldwell, Ruth B. / Role of IL-6 in angiotensin II-induced retinal vascular inflammation. In: Investigative Ophthalmology and Visual Science. 2010 ; Vol. 51, No. 3. pp. 1709-1718.
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AU - Zhang, Wenbo

AU - Lee, Dexter L.

AU - Romero, Maritza J.

AU - Nguyen, Doan T.

AU - Al-Shabrawey, Mohamed

AU - Tsai, Nai Tse

AU - Liou, Gregory I.

AU - Brands, Michael W.

AU - Caldwell, Robert W.

AU - Caldwell, Ruth B.

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N2 - Purpose. The production of proinflammatory cytokines has been shown to play a critical role in a variety of retinal vascular diseases. Angiotensin II and VEGF have been implicated in the initiation of vascular inflammation and retinal vascular disease. However, detailed mechanisms of this process and interactions between inflammatory agonists and angiotensin II in promoting retinopathy are poorly understood. The present study was an investigation of the role of interleukin (IL)-6 in angiotensin II-induced retinopathy. Methods. Rats and IL-6-deficient and wild-type mice were treated with angiotensin II or IL-6, and their retinas were analyzed for leukocyte adhesion or for the expression and localization of VEGF or IL-6. Leukocyte adhesion was assayed by concanavalin A labeling. Vascular density was determined by morphometric analysis. NADPH oxidase activity was assayed by dihydroethidium imaging of superoxide. Results. Intravitreal injection of angiotensin II caused increases in IL-6 mRNA and protein and in leukocyte adhesion to the retinal vessels. IL-6 protein was localized to CD11b-positive microglia and macrophage-like cells. Angiotensin II treatment stimulated increases in retinal levels of VEGF expression and NADPH oxidase activity, which were associated with increased surface area and remodeling of the retinal vessels. These effects were blocked by knocking out IL-6. Intravitreal IL-6 directly induced leukocyte adhesion in both wild-type and IL-6-deficient mice. Conclusions. The results indicate that IL-6 expression is essential for angiotensin II-induced increases in retinal VEGF expression, leukostasis, and vascular remodeling. The data suggest a critical role for IL-6 in mediating angiotensin II-induced retinal vascular inflammation and remodeling.

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