Universität zu Köln

Tsaryk, R., Bartholomae, N. M., Simiantonaki, N., Anspach, L., Peters, K., Heilmann, C., Kirkpatrick, C. J. and Proels, F. (2015). Endoplasmic reticulum-resident chaperones modulate the inflammatory and angiogenic responses of endothelial cells. Br. J. Dermatol., 173 (2). S. 416 - 428. HOBOKEN: WILEY-BLACKWELL. ISSN 1365-2133

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Abstract

Background Wound healing depends on a well-balanced regulation of inflammation and angiogenesis. In chronic wounds the healing process is disturbed and inflammation persists. Regulation of wound closure is controlled by transmembrane and extracellular proteins, the folding and maturation of which occur in the endoplasmic reticulum (ER) by ER-resident chaperone machinery. Objectives To study the role of the ER-resident chaperones BiP/Grp78, its cochaperone Mdg1/ERdJ4, and Grp94 in chronic, nonhealing wounds. Methods Immunohistochemical staining of these chaperones in individual human biopsies and investigation of the possible role of BiP and Mdg1 in endothelial cells, focusing on their inflammatory response and angiogenic potential. Results In all chronic wounds investigated, the levels of these ER-resident chaperones were elevated in endothelial cells and leucocytes. The proangiogenic role of BiP has been shown in tumour growth studies before and was confirmed in this study. Proangiogenic activity of the cochaperone Mdg1 has been postulated before but could not be confirmed in this study. The chemokine tumour necrosis factor (TNF)-alpha was shown to trigger the presentation of proinflammatory adhesion molecules and the release of proinflammatory cytokines. Here we show that TNF-alpha does not affect endogenous chaperone levels, but that the ER-resident chaperones BiP and Mdg1 modulate the cellular TNF-alpha-induced proinflammatory response. Conclusions According to the presented data we assume that in chronic wounds upregulated levels of ER-resident chaperones might contribute to persistent inflammation in chronic wounds. Therapies to downregulate chaperone levels might provide a tool that switches the imbalanced chronic wound microenvironment from inflammation to healing.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tsaryk, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartholomae, N. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Simiantonaki, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Anspach, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilmann, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirkpatrick, C. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Proels, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-397215
DOI:	10.1111/bjd.13816
Journal or Publication Title:	Br. J. Dermatol.
Volume:	173
Number:	2
Page Range:	S. 416 - 428
Date:	2015
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1365-2133
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GLUCOSE-REGULATED PROTEINS; WEIBEL-PALADE BODIES; IN-VITRO; ER STRESS; INDUCTION; BIP; ALPHA; DEGRADATION; EXPRESSION; GRP78/BIP Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39721