Purchase this article with an account.
Deniz Hos, Birgit Regenfuss, Felix Bock, Franziska Bucher, Ludwig M. Heindl, Claus Cursiefen; Indirect Modulation of Inflammatory Corneal Lymphangiogenesis by Interleukin-10. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3238.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The role of Interleukin-10 (IL-10), an antiinflammatory and regulatory cytokine, in the regulation of lymphangiogenesis is so far undefined. Therefore, purpose of this study was to investigate the potential involvement of IL-10 in corneal lymphangiogenesis.
In vitro, lymphatic endothelial cells (LECs) were treated with IL-10 and endothelial cell proliferation was assessed by ELISA. The effect of IL-10 on lymphangiogenic growth factor expression by macrophages (peritoneal exudate cells, PECs) was tested by real-time PCR. In vivo, corneal mRNA expression of IL-10 was analyzed in healthy and in inflamed corneas after suture placement. Furthermore, the amount of developing corneal blood and lymphatic vessels was compared in wildtype and IL-10 knockout (IL-10 -/-) mice after suture placement.
In vitro, IL-10 did not directly affect the proliferation of LECs (p=0.59). In PECs, hemangiogenic VEGF-A expression was downregulated (x0.72; p<0.001), whereas lymphangiogenic VEGF-C expression was upregulated after treatment with IL-10 (x1.59; p<0.001). VEGF-D showed no change in expression levels (p=0.98). In vivo, IL-10 expression was not measurable in healthy corneas. However, 2 days after suture placement, IL-10 mRNA was detectable and was further upregulated during later stages of inflammation (7 days after suture placement: x9.12, p<0.001; 14 days after suture placement: x29.53, p<0.001; values in relation to expression after 2 days). 14 days after suture placement, IL-10 -/- mice showed similar hemvascularized areas (p=0.38), whereas lymphvascularized areas were reduced with borderline-significance when compared to wildtype mice (p=0.053).
IL-10 is expressed in the inflamed murine cornea but only marginally affects inflammatory corneal lymphangiogenesis. This effect of IL-10 is presumably indirectly by modulation of macrophage-derived growth factor expression and not directly by interference with LEC proliferation. Our results suggest IL-10 to be involved in the later stages of the vascular wound healing response.
This PDF is available to Subscribers Only