Modulation of Interleukin-12 activity in the presence of heparin

Abstract Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), modulate the functions of numerous cytokines. The aims of this multidisciplinary research were to characterize heparin binding to interleukin-12 (IL-12) and determine the mechanism(s) by which heparin influences IL-12 b...

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Autores principales:	Srinivas Jayanthi, Bhanu prasanth Koppolu, Khue G. Nguyen, Sean G. Smith, Barbara K. Felber, Thallapuranam Krishnaswamy Suresh Kumar, David A. Zaharoff
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e144fa0271714f01b788c20adf60ba9f
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spelling	oai:doaj.org-article:e144fa0271714f01b788c20adf60ba9f2021-12-02T15:05:28ZModulation of Interleukin-12 activity in the presence of heparin10.1038/s41598-017-05382-12045-2322https://doaj.org/article/e144fa0271714f01b788c20adf60ba9f2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05382-1https://doaj.org/toc/2045-2322Abstract Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), modulate the functions of numerous cytokines. The aims of this multidisciplinary research were to characterize heparin binding to interleukin-12 (IL-12) and determine the mechanism(s) by which heparin influences IL-12 bioactivity. Heparin and HS were found to bind human IL-12 (hIL-12) with low micromolar affinity and increase hIL-12 bioactivity by more than 6-fold. Conversely, other GAGs did not demonstrate significant binding, nor did their addition affect hIL-12 bioactivity. Biophysical studies demonstrated that heparin induced only minor conformational changes while size-exclusion chromatography and small angle X-ray scattering studies indicated that heparin induced dimerization of hIL-12. Heparin modestly protected hIL-12 from proteolytic degradation, however, this was not a likely mechanism for increased cytokine activity in vitro. Flow cytometry studies revealed that heparin increased the amount of hIL-12 bound to cell surfaces. Heparin also facilitated hIL-12 binding and signaling in cells in which both hIL-12 receptor subunits were functionally deleted. Results of this study demonstrate a new role for heparin in modulating the biological activity of IL-12.Srinivas JayanthiBhanu prasanth KoppoluKhue G. NguyenSean G. SmithBarbara K. FelberThallapuranam Krishnaswamy Suresh KumarDavid A. ZaharoffNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Srinivas Jayanthi Bhanu prasanth Koppolu Khue G. Nguyen Sean G. Smith Barbara K. Felber Thallapuranam Krishnaswamy Suresh Kumar David A. Zaharoff Modulation of Interleukin-12 activity in the presence of heparin
description	Abstract Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS), modulate the functions of numerous cytokines. The aims of this multidisciplinary research were to characterize heparin binding to interleukin-12 (IL-12) and determine the mechanism(s) by which heparin influences IL-12 bioactivity. Heparin and HS were found to bind human IL-12 (hIL-12) with low micromolar affinity and increase hIL-12 bioactivity by more than 6-fold. Conversely, other GAGs did not demonstrate significant binding, nor did their addition affect hIL-12 bioactivity. Biophysical studies demonstrated that heparin induced only minor conformational changes while size-exclusion chromatography and small angle X-ray scattering studies indicated that heparin induced dimerization of hIL-12. Heparin modestly protected hIL-12 from proteolytic degradation, however, this was not a likely mechanism for increased cytokine activity in vitro. Flow cytometry studies revealed that heparin increased the amount of hIL-12 bound to cell surfaces. Heparin also facilitated hIL-12 binding and signaling in cells in which both hIL-12 receptor subunits were functionally deleted. Results of this study demonstrate a new role for heparin in modulating the biological activity of IL-12.
format	article
author	Srinivas Jayanthi Bhanu prasanth Koppolu Khue G. Nguyen Sean G. Smith Barbara K. Felber Thallapuranam Krishnaswamy Suresh Kumar David A. Zaharoff
author_facet	Srinivas Jayanthi Bhanu prasanth Koppolu Khue G. Nguyen Sean G. Smith Barbara K. Felber Thallapuranam Krishnaswamy Suresh Kumar David A. Zaharoff
author_sort	Srinivas Jayanthi
title	Modulation of Interleukin-12 activity in the presence of heparin
title_short	Modulation of Interleukin-12 activity in the presence of heparin
title_full	Modulation of Interleukin-12 activity in the presence of heparin
title_fullStr	Modulation of Interleukin-12 activity in the presence of heparin
title_full_unstemmed	Modulation of Interleukin-12 activity in the presence of heparin
title_sort	modulation of interleukin-12 activity in the presence of heparin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e144fa0271714f01b788c20adf60ba9f
work_keys_str_mv	AT srinivasjayanthi modulationofinterleukin12activityinthepresenceofheparin AT bhanuprasanthkoppolu modulationofinterleukin12activityinthepresenceofheparin AT khuegnguyen modulationofinterleukin12activityinthepresenceofheparin AT seangsmith modulationofinterleukin12activityinthepresenceofheparin AT barbarakfelber modulationofinterleukin12activityinthepresenceofheparin AT thallapuranamkrishnaswamysureshkumar modulationofinterleukin12activityinthepresenceofheparin AT davidazaharoff modulationofinterleukin12activityinthepresenceofheparin
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Modulation of Interleukin-12 activity in the presence of heparin

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