Universität zu Köln

Dantas, Rafael L., Brachvogel, Bent, Schied, Tanja, Bergmeier, Vera, Skryabin, Boris, Vogl, Thomas, Ludwig, Stephan ORCID: 0000-0003-4490-3052 and Wixler, Viktor (2017). The LIM-Only Protein Four and a Half LIM Domain Protein 2 Attenuates Development of Psoriatic Arthritis by Blocking Adam17-Mediated Tumor Necrosis Factor Release. Am. J. Pathol., 187 (11). S. 2388 - 2399. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

Four and a half LIM domain protein 2 (Fhl2) is an intracellular adaptor molecule with a high protein protein interaction capacity. It acts as a modulator of several signaling molecules in the cytosol and as a cofactor of transcription in the nucleus. Recent studies suggest the role of Fhl2 in tissue repair and the anti-inflammatory response. Herein, we show that Fhl2-deficient mice develop a more severe psoriatic arthritis disease under induction of the inducible human tumor necrosis factor (hTNF) transgene than wild-type mice. The disease was accompanied by increased infiltration of activated macrophages and T regulatory cells in skin and digit joints as well as by increased expression of matrix metalloproteases and bone-specific proteases. The more severe pathogenesis of psoriatic arthritis in Fhl2 knockout mice coincided with enhanced Levels of soluble hTNF cytokine, but surprisingly not with transcription of the hTNF transgene. Studying the shedding of cell membrane bound hTNF by Adam17, a known Fhl2 interacting protein, revealed an enhanced release of TNF in the absence of Fhl2. In summary, our results show that Fhl2 anticipates the emerging inflammation and specifically the development of psoriatic arthritis by impeding the Adam17-mediated release of TNF.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dantas, Rafael L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED Schied, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmeier, Vera UNSPECIFIED UNSPECIFIED UNSPECIFIED Skryabin, Boris UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogl, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Ludwig, Stephan UNSPECIFIED orcid.org/0000-0003-4490-3052 UNSPECIFIED Wixler, Viktor UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-213213
DOI:	10.1016/j.ajpath.2017.07.015
Journal or Publication Title:	Am. J. Pathol.
Volume:	187
Number:	11
Page Range:	S. 2388 - 2399
Date:	2017
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 MATRIX METALLOPROTEINASES; FACTOR-ALPHA; FHL2; DEFICIENCY; CELLS; CYTOSKELETON; INFLAMMATION; EXPRESSION; CANCER; TISSUE Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21321