Universität zu Köln

Hos, Deniz, Bucher, Franziska, Regenfuss, Birgit, Dreisow, Marie-Luise, Bock, Felix, Heindl, Ludwig M., Eming, Sabine A. and Cursiefen, Claus (2016). IL-10 Indirectly Regulates Corneal Lymphangiogenesis and Resolution of Inflammation via Macrophages. Am. J. Pathol., 186 (1). S. 159 - 172. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

The role of IL-10, a primarily anti-inflammatory cytokine, in the regulation of inflammatory lymphangiogenesis is undetermined. Herein, we show that IL-10 modulates corneal Lymphangiogenesis and resolution of inflammation. IL-10 was not expressed in healthy corneas but was up-regulated in inflamed corneas by infiltrating macrophages. Macrophages up-regulated the expression of prolymphangiogenic vascular endothelial growth factor-C upon stimulation with IL-10. Consistently, corneal inflammation resulted in reduced expression of vascular endothelial growth factor-C and decreased corneal Lymphangiogenesis in IL-10 deficient mice (IL-10(-/-)). The effect of IL-10 on Lymphangiogenesis was indirect via macrophages, because IL-10 did not directly affect Lymphatic endothelial cells. The expression of proinflammatory cytokines and the numbers of infiltrating macrophages increased and remained elevated in inflamed corneas of IL-10(-/-) mice, indicating that IL-10 deficiency Led to more severe and prolonged inflammation. The corneal phenotype of IL-10 deficient mice was mimicked in mice with conditional deletion of Stat3 in myeloid cells (Lysozyme M Cre mice Stat(fL/fL) mice), corroborating the critical rote of macrophages in the regulation of lymphangiogenesis. Furthermore, Local treatment with IL-10 promoted Lymphangiogenesis and faster egress of macrophages from inflamed corneas. Taken together, we demonstrate that IL-10 indirectly regulates inflammatory corneal Lymphangiogenesis via macrophages. Reduced Lymphangiogenesis in IL-10(-/-) and lysozyme M Cre Stat3(fL/fL) mice is associated with more severe inflammatory responses, whereas IL-10 treatment results in faster resolution of inflammation. IL-10 might be used therapeutically to terminate pathological inflammation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hos, Deniz UNSPECIFIED UNSPECIFIED UNSPECIFIED Bucher, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Regenfuss, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreisow, Marie-Luise UNSPECIFIED UNSPECIFIED UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Heindl, Ludwig M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cursiefen, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-292213
DOI:	10.1016/j.ajpath.2015.09.012
Journal or Publication Title:	Am. J. Pathol.
Volume:	186
Number:	1
Page Range:	S. 159 - 172
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1525-2191
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR RECEPTOR-3; IN-VIVO; LYVE-1-POSITIVE MACROPHAGES; LYMPHATIC VASCULATURE; BOWEL-DISEASE; ACTIVATION; MICE; ANGIOGENESIS; INTERLEUKIN-10; BLOCKADE Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29221