IL-17A exacerbates diabetic retinopathy by impairing Müller cell function via Act1 signaling
Experimental & Molecular Medicine
;
: e280-2016.
Article
in English
| WPRIM
| ID: wpr-149851
ABSTRACT
Diabetic retinopathy (DR), one of the most serious complications of diabetes, has been associated with inflammatory processes. We have recently reported that interleukin (IL)-17A, a proinflammatory cytokine, is increased in the plasma of diabetic patients. Further investigation is required to clarify the role of IL-17A in DR. Ins2(Akita) (Akita) diabetic mice and high-glucose (HG)-treated primary Müller cells were used to mimic DR-like pathology. Diabetes induced retinal expression of IL-17A and IL-17 receptor A (IL-17RA) in Müller cells in contrast to ganglion cells. Further evidence demonstrated that retinal Müller cells cultured in vitro increased IL-17A and IL-17RA expression as well as IL-17A secretion in the HG condition. In both the HG-treated Müller cells and Akita mouse retina, the Act1/TRAF6/IKK/NF-κB signaling pathway was activated. IL-17A further enhanced inflammatory signaling activation, whereas Act1 knockdown or IKK inhibition blocked the downstream signaling activation by IL-17A. HG- and diabetes-induced Müller cell activation and dysfunction, as determined by increased glial fibrillary acidic protein, vascular endothelial growth factor and glutamate levels and decreased glutamine synthetase and excitatory amino acid transporter-1 expression, were exacerbated by IL-17A; however, they were alleviated by Act1 knockdown or IKK inhibition. In addition, IL-17A intravitreal injection aggravated diabetes-induced retinal vascular leukostasis, vascular leakage and ganglion cell apoptosis, whereas Act1 silencing or anti-IL-17A monoclonal antibody ameliorated the retinal vascular damage and neuronal cell apoptosis. These findings establish that IL-17A exacerbates DR-like pathology by the promotion of Müller cell functional impairment via Act1 signaling.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Plasma
/
Retina
/
Retinaldehyde
/
In Vitro Techniques
/
Interleukins
/
Apoptosis
/
Glutamic Acid
/
Excitatory Amino Acids
/
Leukostasis
Limits:
Animals
/
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2016
Type:
Article
Similar
MEDLINE
...
LILACS
LIS