TY  - JOUR
A1  - Seher, Axel
A1  - Nickel, Joachim
A1  - Mueller, Thomas D.
A1  - Kneitz, Susanne
A1  - Gebhardt, Susanne
A1  - Meyer ter Vehn, Tobias
A1  - Schlunck, Guenther
A1  - Sebald, Walter
T1  - Gene expression profiling of connective tissue growth factor (CTGF) stimulated primary human tenon fibroblasts reveals an inflammatory and wound healing response in vitro
JF  - Molecular Vision
N2  - Purpose: 

The biologic relevance of human connective tissue growth factor (hCTGF) for primary human tenon fibroblasts (HTFs) was investigated by RNA expression profiling using affymetrix (TM) oligonucleotide array technology to identify genes that are regulated by hCTGF. 

Methods: 

Recombinant hCTGF was expressed in HEK293T cells and purified by affinity and gel chromatography. Specificity and biologic activity of hCTGF was confirmed by biosensor interaction analysis and proliferation assays. For RNA expression profiling HTFs were stimulated with hCTGF for 48h and analyzed using affymetrix (TM) oligonucleotide array technology. Results were validated by real time RT-PCR. 

Results: 

hCTGF induces various groups of genes responsible for a wound healing and inflammatory response in HTFs. A new subset of CTGF inducible inflammatory genes was discovered (e.g., chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-X-C motif] ligand 6 [CXCL6], interleukin 6 [IL6], and interleukin 8 [IL8]). We also identified genes that can transmit the known biologic functions initiated by CTGF such as proliferation and extracellular matrix remodelling. Of special interest is a group of genes, e.g., osteoglycin (OGN) and osteomodulin (OMD), which are known to play a key role in osteoblast biology. 

Conclusions: 

This study specifies the important role of hCTGF for primary tenon fibroblast function. The RNA expression profile yields new insights into the relevance of hCTGF in influencing biologic processes like wound healing, inflammation, proliferation, and extracellular matrix remodelling in vitro via transcriptional regulation of specific genes. The results suggest that CTGF potentially acts as a modulating factor in inflammatory and wound healing response in fibroblasts of the human eye.
KW  - Bone morphogenetic protein-2
KW  - Smooth-muscle-cells
KW  - Myofibroblast differentiation
KW  - TGF-beta
KW  - CYR61
KW  - Proliferation
KW  - Mechanisms
KW  - Apoptosis
KW  - Receptor
KW  - Cancer
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140189
VL  - 17
IS  - 08. Okt
ER  - 
TY  - JOUR
A1  - Silva-Vilches, Cinthia
A1  - Pletinckx, Katrien
A1  - Lohnert, Miriam
A1  - Pavlovic, Vladimir
A1  - Ashour, Diyaaeldin
A1  - John, Vini
A1  - Vendelova, Emilia
A1  - Kneitz, Susanne
A1  - Zhou, Jie
A1  - Chen, Rena
A1  - Reinheckel, Thomas
A1  - Mueller, Thomas D.
A1  - Bodem, Jochen
A1  - Lutz, Manfred B.
T1  - Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion
JF  - PLoS ONE
N2  - Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3\(^{+}\) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT\(^{hi}\), CT\(^{lo}\)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT\(^{hi}\) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT\(^{lo}\)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3\(^{+}\) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT\(^{lo}\)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3\(^{+}\) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.
KW  - small interfering RNAs
KW  - toxins
KW  - regulatory T cells
KW  - T cells
KW  - cytokines
KW  - cholera
KW  - cell differentiation
KW  - immune evasion
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158244
VL  - 12
IS  - 7
ER  -