TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood

Mohammad Abul Kashem,1– 4 Xin-Yong Yuan,4 Lin Li,2 Joshua Kimani,5 Francis Plummer1 ,† Ma Luo1,2,4 1Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada; 2JC Wilt Infectious Diseases Research Centre, Winnipeg, Mb, Canada; 3Department of Microbiolog...

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Autores principales:	Kashem MA, Yuan XY, Li L, Kimani J, Plummer F, Luo M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	tilrr soluble biomarker human plasma mouse anti-frem1 mabs multiplex bead array method western blot analysis. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/230d51c42ff749e8a590c2458ac0392d
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spelling	oai:doaj.org-article:230d51c42ff749e8a590c2458ac0392d2021-12-02T17:27:13ZTILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood1178-7031https://doaj.org/article/230d51c42ff749e8a590c2458ac0392d2021-09-01T00:00:00Zhttps://www.dovepress.com/tilrr-toll-like-interleukin-1-receptor-regulator-an-important-modulato-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Mohammad Abul Kashem,1– 4 Xin-Yong Yuan,4 Lin Li,2 Joshua Kimani,5 Francis Plummer1 ,† Ma Luo1,2,4 1Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada; 2JC Wilt Infectious Diseases Research Centre, Winnipeg, Mb, Canada; 3Department of Microbiology and Veterinary Public Health, Chittagong Veterinary and Animal Sciences University, Chittagong, Bangladesh; 4National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; 5Institute for Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya†In memoriam (passed away on February 4, 2020).Correspondence: Ma LuoDepartment of Medical Microbiology, University of Manitoba, Winnipeg, MB, CanadaTel +204-789-5072Fax +204-789-2018Email maluo@canada.ca; Ma.Luo@umanitoba.caPurpose: TILRR (Toll-like interleukin-1 receptor regulator), a variant of FREM1 (Fras-related extracellular matrix 1), is a modulator of many genes in NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling and inflammatory responses. It enhanced the expression of multiple genes in the NF-κB signaling pathway and promoted the production of multiple pro-inflammatory cytokines/chemokines. TILRR is an extracellular matrix protein and expressed in cells and tissues, and has never been considered to exist in the blood. The study aimed to identify circulating TILRR protein in human plasma as a biomarker of systemic inflammation.Methods and Results: We developed a multiplex bead array method (Bio-Plex) using 4 monoclonal antibodies targeting different protein domains of FREM1/TILRR to investigate whether TILRR can be detected in blood plasma. The results of the multiplex bead array method were validated by Western blot analysis of affinity-purified TILRR from patient plasma samples. We subsequently analyzed 640 plasma samples from women enrolled in the Pumwani Sex Worker cohort (PSWC) (Nairobi, Kenya). Our study showed that TILRR exists in all patient plasma samples, but its quantities vary greatly among the patients, ranging from 2.38 ng/mL to 5196.79 ng/mL. The plasma TILRR below 2.38 ng/mL can only be detected by affinity purification and Western blot analysis.Conclusion: Our in-house developed multiplex bead array method can successfully quantify TILRR protein in plasma samples. Because TILRR is an important modulator of many inflammation-responsive genes, it may be an inflammation biomarker in blood and play a role in modulating systemic inflammation.Keywords: TILRR, soluble biomarker, human plasma, mouse anti-FREM1 mAbs, multiplex bead array method, Western blot analysisKashem MAYuan XYLi LKimani JPlummer FLuo MDove Medical Pressarticletilrrsoluble biomarkerhuman plasmamouse anti-frem1 mabsmultiplex bead array methodwestern blot analysis.PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4927-4943 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tilrr soluble biomarker human plasma mouse anti-frem1 mabs multiplex bead array method western blot analysis. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	tilrr soluble biomarker human plasma mouse anti-frem1 mabs multiplex bead array method western blot analysis. Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Kashem MA Yuan XY Li L Kimani J Plummer F Luo M TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood
description	Mohammad Abul Kashem,1– 4 Xin-Yong Yuan,4 Lin Li,2 Joshua Kimani,5 Francis Plummer1 ,† Ma Luo1,2,4 1Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada; 2JC Wilt Infectious Diseases Research Centre, Winnipeg, Mb, Canada; 3Department of Microbiology and Veterinary Public Health, Chittagong Veterinary and Animal Sciences University, Chittagong, Bangladesh; 4National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; 5Institute for Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya†In memoriam (passed away on February 4, 2020).Correspondence: Ma LuoDepartment of Medical Microbiology, University of Manitoba, Winnipeg, MB, CanadaTel +204-789-5072Fax +204-789-2018Email maluo@canada.ca; Ma.Luo@umanitoba.caPurpose: TILRR (Toll-like interleukin-1 receptor regulator), a variant of FREM1 (Fras-related extracellular matrix 1), is a modulator of many genes in NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling and inflammatory responses. It enhanced the expression of multiple genes in the NF-κB signaling pathway and promoted the production of multiple pro-inflammatory cytokines/chemokines. TILRR is an extracellular matrix protein and expressed in cells and tissues, and has never been considered to exist in the blood. The study aimed to identify circulating TILRR protein in human plasma as a biomarker of systemic inflammation.Methods and Results: We developed a multiplex bead array method (Bio-Plex) using 4 monoclonal antibodies targeting different protein domains of FREM1/TILRR to investigate whether TILRR can be detected in blood plasma. The results of the multiplex bead array method were validated by Western blot analysis of affinity-purified TILRR from patient plasma samples. We subsequently analyzed 640 plasma samples from women enrolled in the Pumwani Sex Worker cohort (PSWC) (Nairobi, Kenya). Our study showed that TILRR exists in all patient plasma samples, but its quantities vary greatly among the patients, ranging from 2.38 ng/mL to 5196.79 ng/mL. The plasma TILRR below 2.38 ng/mL can only be detected by affinity purification and Western blot analysis.Conclusion: Our in-house developed multiplex bead array method can successfully quantify TILRR protein in plasma samples. Because TILRR is an important modulator of many inflammation-responsive genes, it may be an inflammation biomarker in blood and play a role in modulating systemic inflammation.Keywords: TILRR, soluble biomarker, human plasma, mouse anti-FREM1 mAbs, multiplex bead array method, Western blot analysis
format	article
author	Kashem MA Yuan XY Li L Kimani J Plummer F Luo M
author_facet	Kashem MA Yuan XY Li L Kimani J Plummer F Luo M
author_sort	Kashem MA
title	TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood
title_short	TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood
title_full	TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood
title_fullStr	TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood
title_full_unstemmed	TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood
title_sort	tilrr (toll-like interleukin-1 receptor regulator), an important modulator of inflammatory responsive genes, is circulating in the blood
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/230d51c42ff749e8a590c2458ac0392d
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TILRR (Toll-like Interleukin-1 Receptor Regulator), an Important Modulator of Inflammatory Responsive Genes, is Circulating in the Blood

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