Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782409330058854400 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4707532 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT iqbalsm lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT leonardc lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT cregmis lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT derantered lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT tailorp lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT reng lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT ishidah lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT hsucy lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT abubackers lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT pangdsj lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT tsalop lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT vogelhj lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT hartda lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT waterhousecc lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT jaygd lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT schmidtta lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro AT krawetzrj lubricinproteoglycan4bindstoandregulatestheactivityoftolllikereceptorsinvitro |