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Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro

Proteoglycan 4 (PRG4/lubricin) is secreted by cells that reside in articular cartilage and line the synovial joint. Lubricin may play a role in modulating inflammatory responses through interaction with CD44. This led us to examine if lubricin could be playing a larger role in the modulation of infl...

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Autores principales: Iqbal, S.M., Leonard, C., C. Regmi, S., De Rantere, D., Tailor, P., Ren, G., Ishida, H., Hsu, CY., Abubacker, S., Pang, D. SJ., T. Salo, P., Vogel, H.J., Hart, D.A., Waterhouse, C.C., Jay, G.D, Schmidt, T.A., Krawetz, R.J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707532/
https://www.ncbi.nlm.nih.gov/pubmed/26752378
http://dx.doi.org/10.1038/srep18910
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author Iqbal, S.M.
Leonard, C.
C. Regmi, S.
De Rantere, D.
Tailor, P.
Ren, G.
Ishida, H.
Hsu, CY.
Abubacker, S.
Pang, D. SJ.
T. Salo, P.
Vogel, H.J.
Hart, D.A.
Waterhouse, C.C.
Jay, G.D
Schmidt, T.A.
Krawetz, R.J.
author_facet Iqbal, S.M.
Leonard, C.
C. Regmi, S.
De Rantere, D.
Tailor, P.
Ren, G.
Ishida, H.
Hsu, CY.
Abubacker, S.
Pang, D. SJ.
T. Salo, P.
Vogel, H.J.
Hart, D.A.
Waterhouse, C.C.
Jay, G.D
Schmidt, T.A.
Krawetz, R.J.
author_sort Iqbal, S.M.
collection PubMed
description Proteoglycan 4 (PRG4/lubricin) is secreted by cells that reside in articular cartilage and line the synovial joint. Lubricin may play a role in modulating inflammatory responses through interaction with CD44. This led us to examine if lubricin could be playing a larger role in the modulation of inflammation/immunity through interaction with Toll-like receptors (TLRs). Human Embryonic Kidney (HEK) cells overexpressing TLRs 2, 4 or 5 and surface plasmon resonance were employed to determine if full length recombinant human lubricin was able to bind to and activate TLRs. Primary human synovial fibroblasts were also examined using flow cytometry and Luminex multiplex ELISA. A rat destabilization model of osteoarthritis (OA) was used to determine if lubricin injections were able to regulate pain and/or inflammation in vivo. Lubricin can bind to and regulate the activity of TLRs, leading to downstream changes in inflammatory signalling independent of HA. We confirmed these findings in vivo through intra-articular injections of lubricin in a rat OA model where the inhibition of systemic inflammatory signaling and reduction in pain were observed. Lubricin plays an important role in regulating the inflammatory environment under both homeostatic and tissue injury states.
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spelling pubmed-47075322016-01-20 Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro Iqbal, S.M. Leonard, C. C. Regmi, S. De Rantere, D. Tailor, P. Ren, G. Ishida, H. Hsu, CY. Abubacker, S. Pang, D. SJ. T. Salo, P. Vogel, H.J. Hart, D.A. Waterhouse, C.C. Jay, G.D Schmidt, T.A. Krawetz, R.J. Sci Rep Article Proteoglycan 4 (PRG4/lubricin) is secreted by cells that reside in articular cartilage and line the synovial joint. Lubricin may play a role in modulating inflammatory responses through interaction with CD44. This led us to examine if lubricin could be playing a larger role in the modulation of inflammation/immunity through interaction with Toll-like receptors (TLRs). Human Embryonic Kidney (HEK) cells overexpressing TLRs 2, 4 or 5 and surface plasmon resonance were employed to determine if full length recombinant human lubricin was able to bind to and activate TLRs. Primary human synovial fibroblasts were also examined using flow cytometry and Luminex multiplex ELISA. A rat destabilization model of osteoarthritis (OA) was used to determine if lubricin injections were able to regulate pain and/or inflammation in vivo. Lubricin can bind to and regulate the activity of TLRs, leading to downstream changes in inflammatory signalling independent of HA. We confirmed these findings in vivo through intra-articular injections of lubricin in a rat OA model where the inhibition of systemic inflammatory signaling and reduction in pain were observed. Lubricin plays an important role in regulating the inflammatory environment under both homeostatic and tissue injury states. Nature Publishing Group 2016-01-11 /pmc/articles/PMC4707532/ /pubmed/26752378 http://dx.doi.org/10.1038/srep18910 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Iqbal, S.M.
Leonard, C.
C. Regmi, S.
De Rantere, D.
Tailor, P.
Ren, G.
Ishida, H.
Hsu, CY.
Abubacker, S.
Pang, D. SJ.
T. Salo, P.
Vogel, H.J.
Hart, D.A.
Waterhouse, C.C.
Jay, G.D
Schmidt, T.A.
Krawetz, R.J.
Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro
title Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro
title_full Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro
title_fullStr Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro
title_full_unstemmed Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro
title_short Lubricin/Proteoglycan 4 binds to and regulates the activity of Toll-Like Receptors In Vitro
title_sort lubricin/proteoglycan 4 binds to and regulates the activity of toll-like receptors in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707532/
https://www.ncbi.nlm.nih.gov/pubmed/26752378
http://dx.doi.org/10.1038/srep18910
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