Interleukin-17A neutralization alleviated ocular neovascularization by promoting
M2 and mitigating M1 macrophage polarization
#MMPMID26694999
Zhu Y
; Tan W
; Demetriades AM
; Cai Y
; Gao Y
; Sui A
; Lu Q
; Shen X
; Jiang C
; Xie B
; Sun X
Immunology
2016[Apr]; 147
(4
): 414-28
PMID26694999
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Neovascularization (NV), as a cardinal complication of several ocular diseases,
has been intensively studied, and research has shown its close association with
inflammation and immune cells. In the present study, the role of interleukin-17A
(IL-17A) in angiogenesis in the process of ocular NV both in vivo and in vitro
was investigated. Also, a paracrine role of IL-17A was demonstrated in the
crosstalk between endothelial cells and macrophages in angiogenesis. In the
retinas of mice with retinopathy of prematurity, the IL-17A expression increased
significantly at postnatal day 15 (P15) and P18 during retinal NV. Mice given
IL-17A neutralizing antibody (NAb) developed significantly reduced choroidal NV
and retinal NV. Studies on vascular endothelial growth factor (VEGF)
over-expressing mice suggested that IL-17A modulated NV through the VEGF pathway.
Furthermore, IL-17A deficiency shifted macrophage polarization toward an M2
phenotype during retinal NV with significantly reduced M1 cytokine expression
compared with wild-type controls. In vitro assays revealed that IL-17A treated
macrophage supernatant gave rise to elevated human umbilical vascular endothelial
cell proliferation, tube formation and VEGF receptor 1 and receptor 2 expression.
Therefore, IL-17A could potentially serve as a novel target for treating ocular
NV diseases. The limitation of this study involved the potential mechanisms, such
as which transcription accounted for macrophage polarization and how the
subsequent cytokines were modulated when macrophages were polarized. Further
studies need to be undertaken to definitively determine the extent to which
IL-17A neutralizing anti-angiogenic activity depends on macrophage modulation
compared with anti-VEGF treatment.
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