TY  - JOUR
A1  - Hsieh, Louise Tzung-Harn
A1  - Năstase, Mădălina-Viviana
A1  - Rödig, Heiko
A1  - Zeng-Brouwers, Jinyang
A1  - Poluzzi, Chiara
A1  - Schwalm, Stephanie
A1  - Fork, Christian
A1  - Tredup, Claudia
A1  - Brandes, Ralf
A1  - Wygrecka, Malgorzata
A1  - Huwiler, Andrea
A1  - Pfeilschifter, Josef
A1  - Schäfer, Liliana
T1  - Biglycan- and sphingosine kinase-1 signaling crosstalk regulates the synthesis of macrophage chemoattractants
T2  - International journal of molecular sciences
N2  - In its soluble form, the extracellular matrix proteoglycan biglycan triggers the synthesis of the macrophage chemoattractants, chemokine (C-C motif) ligand CCL2 and CCL5 through selective utilization of Toll-like receptors (TLRs) and their adaptor molecules. However, the respective downstream signaling events resulting in biglycan-induced CCL2 and CCL5 production have not yet been defined. Here, we show that biglycan stimulates the production and activation of sphingosine kinase 1 (SphK1) in a TLR4- and Toll/interleukin (IL)-1R domain-containing adaptor inducing interferon (IFN)-β (TRIF)-dependent manner in murine primary macrophages. We provide genetic and pharmacological proof that SphK1 is a crucial downstream mediator of biglycan-triggered CCL2 and CCL5 mRNA and protein expression. This is selectively driven by biglycan/SphK1-dependent phosphorylation of the nuclear factor NF-κB p65 subunit, extracellular signal-regulated kinase (Erk)1/2 and p38 mitogen-activated protein kinases. Importantly, in vivo overexpression of soluble biglycan causes Sphk1-dependent enhancement of renal CCL2 and CCL5 and macrophage recruitment into the kidney. Our findings describe the crosstalk between biglycan- and SphK1-driven extracellular matrix- and lipid-signaling. Thus, SphK1 may represent a new target for therapeutic intervention in biglycan-evoked inflammatory conditions.
KW  - damage-associated molecular pattern
KW  - small leucine-rich proteoglycan
KW  - toll-like receptors
KW  - chemoattractant
KW  - extracellular matrix
KW  - lipid signaling
KW  - sphingolipid
KW  - macrophage
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/44064
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-440646
SN  - 1422-0067
SN  - 1661-6596
N1  - © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
VL  - 18
IS  - 3, Art. 595
SP  - 1
EP  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -