TY  - JOUR
A1  - Brosinsky, Paulin
A1  - Leister, Hanna
A1  - Cheng, Nan
A1  - Varelas, Xaralabos
A1  - Visekruna, Alexander
A1  - Luu, Maik
T1  - Verteporfin protects against Th17 cell‐mediated EAE independently of YAP inhibition
JF  - European Journal of Immunology
N2  - The known YAP inhibitor verteporfin is capable of repressing IL‐17A production in Th17 cells. However, this effect is mediated independently of YAP and can ameliorate Th17‐mediated experimental autoimmune encephalomyelitis (EAE) upon in vivo administration. The data suggest verteprofin's mode of action for the design of novel therapeutic autoimmune disease intervention.
KW  - Hippo signaling
KW  - YAP
KW  - verteporfin
KW  - Th17 cells
KW  - EAE
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287234
VL  - 52
IS  - 9
SP  - 1523
EP  - 1526
ER  - 
TY  - JOUR
A1  - Rajendran, Ranjithkumar
A1  - Rajendran, Vinothkumar
A1  - Gupta, Liza
A1  - Shirvanchi, Kian
A1  - Schunin, Darja
A1  - Karnati, Srikanth
A1  - Giraldo-Velásquez, Mario
A1  - Berghoff, Martin
T1  - Interferon beta-1a versus combined interferon beta-1a and oligodendrocyte-specific FGFR1 deletion in experimental autoimmune encephalomyelitis
JF  - International Journal of Molecular Sciences
N2  - Recombinant beta interferons-1 (IFNβ-1) are used as first line therapies in patients with relapsing multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease of the CNS. IFNβ-1a/b has moderate effects on the prevention of relapses and slowing of disease progression. Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) are known to play a key role in the pathology of MS and its model EAE. To investigate the effects of short-term treatment with s.c. IFNβ-1a versus the combined application of s.c. IFNβ-1a and oligodendrocyte-specific deletion of FGFR1 (Fgfr1\(^{ind−/−}\) mice) in MOG\(_{35-55}\)-induced EAE. IFNβ-1a (30 mg/kg) was applied s.c. from days 0–7 p.i. of EAE in controls and Fgfr1\(^{ind−/−}\) mice. FGFR signaling proteins associated with inflammation/degeneration in MS/EAE were analyzed by western blot in the spinal cord. Further, FGFR1 in Oli-neu oligodendrocytes were inhibited by PD166866 and treated with IFNβ-1a (400 ng/mL). Application of IFNβ-1a over 8 days resulted in less symptoms only at the peak of disease (days 9–11) compared to controls. Application of IFNβ-1a in Fgfr1\(^{ind−/−}\) mice resulted in less symptoms primarily in the chronic phase of EAE. Fgfr1\(^{ind−/−}\) mice treated with IFNβ-1a showed increased expression of pERK and BDNF. In Oli-neu oligodendrocytes, treatment with PD166866 and IFNβ-1a also showed an increased expression of pERK and BDNF/TrkB. These data suggest that the beneficial effects in the chronic phase of EAE and on signaling molecules associated with ERK and BDNF expression are caused by the modulation of FGFR1 and not by interferon beta-1a. FGFR may be a potential target for therapy in MS.
KW  - FGFR1
KW  - interferon beta-1a
KW  - oligodendrocytes
KW  - EAE
KW  - multiple sclerosis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290401
SN  - 1422-0067
VL  - 23
IS  - 20
ER  -