Biglycan is a new high-affinity ligand for CD14 in macrophages

Matrix Biology : Journal of the International Society for Matrix Biology
Heiko RoedigLiliana Schaefer

Abstract

Sterile inflammation is a therapeutic target in many diseases where it represents an important initiator of disease progression. However, the detailed mechanisms underlying its evolution and biological relevance are not yet completely elucidated. Biglycan, a prototype extracellular matrix-derived damage-associated molecular pattern, mediates sterile inflammation in macrophages through Toll-like receptor (TLR) 2 and/or TLR4-dependent signaling pathways. Here we discovered that soluble biglycan is a novel high-affinity ligand for CD14, a well-known GPI-anchored co-receptor for TLRs. CD14 is required for all biglycan-mediated TLR2/4 dependent inflammatory signaling pathways in macrophages. By binding to CD14 and choosing different TLR signaling branches, biglycan induced TNF-α and CCL2 via TLR2/4, HSP70 through TLR2, and CCL5 via TLR4. Mechanistically, biglycan evoked phosphorylation and subsequent nuclear translocation of p38, p44/42, and NF-κB, and these effects were due to a specific, high-affinity interaction between biglycan protein core and CD14. Finally, we provide proof-of-principle for the requirement of CD14, by transiently overexpressing biglycan in a mouse model of renal ischemia/reperfusion injury performed in Cd14-/-...Continue Reading

Citations

Jul 7, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Jinyang Zeng-BrouwersLiliana Schaefer
Dec 20, 2018·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Mareike BarthArtur Lichtenberg
May 10, 2019·Frontiers in Immunology·George TzanakakisDragana Nikitovic
Dec 12, 2020·Experimental Biology and Medicine·Aric F LogsdonMichelle A Erickson
Nov 2, 2019·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Michele ScuruchiGiuseppe Mandraffino
Nov 7, 2019·Cellular Signalling·Matthias KrämerMalgorzata Wygrecka
Mar 3, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Shiju YeGuang Liang
Apr 4, 2021·Animals : an Open Access Journal From MDPI·Joanna JaworskaMarta Siemieniuch
Apr 17, 2021·Journal of Cell Communication and Signaling·Norio MatsushimaRobert H Kretsinger
Jun 29, 2021·Molecular and Cellular Biochemistry·Sandeep AppunniAlpana Sharma
Jun 13, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Martin SchulzLiliana Schaefer

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