Angptl2 mediates intraocular inflammation by activating Müller cells through PirB

Abstract

Objective To investigate the pro-inflammatory effects and mechanisms of angiopoietin-like protein 2 (Angptl2) in the eyes. Methods SD rats (8 weeks old) were given a single intravitreal injection of 0.2 mg LPS or PBS to establish intraocular inflammation model or sham operation. Then the Angptl2 expression in the retina was examined by real-time PCR (RT-PCR). Müller cells were isolated from the retina of newborn SD rats (with 24 h after born). After the obtained cells were purified and identified, the recombinant Angptl2 was added to the primarily cultured cells. Cell count, immunofluorescence assay and RT-PCR were used to assess the proliferation of Müller cells, the expression of GFAP, and levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α), respectively. The expression of Angptl2 ligand, paired immunoglobulin-like receptor B (PirB), in the Müller cells was observed by immunofluorescence assay. RT-PCR was employed to observed the expression of IL-6 and TNF-α in the Müller cells of PBS group, Angptl2 group, Ad-C (transfection of adenovirus negative control Ad-C)+Angptl2 group, and Ad-PirB-siRNA (transfection of adenovirus Ad-PirB-siRNA)+Angptl2 group. Results The mRNA level of Angptl2 was increased notably in the retina of the LPS-treated rats (intraocular inflammation model) than the control rats (P < 0.05). Exogenous Angptl2 treatment resulted in higher proliferation rate, expression of GFAP and the levels of IL-1β, IL-6 and TNF-α in Müller cells (P < 0.05). PirB was expressed in the retinal Müller cells. Interference of PirB by adenovirus Ad-PirB-siRNA significantly decreased the levels of IL-6 and TNF-α (P < 0.05). Conclusion Angptl2 mediates acute intraocular inflammation by activating Müller cells to secrets IL-1β, IL-6 and TNF-α though PirB.

Keywords

• angiopoietin-like protein 2
• paired immunoglobulin-like receptor b
• retina
• müller cells
• inflammation