Staff View: LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells

LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells

Background: Although promising for graft-versus-host disease (GvHD) treatment, MSC therapy still faces important challenges. For instance, increasing MSC migratory capacity as well as potentializing immune response suppression are of interest. For GvHD management, preventing opportunistic infections...

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Main Authors:	Bravo, Martha Oliveira, Sangiorgi, Bruno Braga, Schiavinato, Josiane Lilian dos Santos, Carvalho, Juliana Lott, Covas, Dimas Tadeu, Panepucci, Rodrigo Alexandre, Neves, Francisco de Assis Rocha, Franco, Octávio Luiz, Pereira, Rinaldo Wellerson, Araujo, Felipe Saldanha de
Format:	Artigo
Language:	Inglês
Published:	BioMed Central 2017
Subjects:	Peptídeos Imunologia
Online Access:	http://repositorio.unb.br/handle/10482/23870 https://dx.doi.org/10.1186/s13287-016-0448-3
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spelling	ir-10482-238702020-10-13T17:43:12Z LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells Bravo, Martha Oliveira Sangiorgi, Bruno Braga Schiavinato, Josiane Lilian dos Santos Carvalho, Juliana Lott Covas, Dimas Tadeu Panepucci, Rodrigo Alexandre Neves, Francisco de Assis Rocha Franco, Octávio Luiz Pereira, Rinaldo Wellerson Araujo, Felipe Saldanha de Peptídeos Imunologia Background: Although promising for graft-versus-host disease (GvHD) treatment, MSC therapy still faces important challenges. For instance, increasing MSC migratory capacity as well as potentializing immune response suppression are of interest. For GvHD management, preventing opportunistic infections is also a valuable strategy, since immunocompromised patients are easy targets for infections. LL-37 is a host defense peptide (HDP) that has been deeply investigated due to its immunomodulatory function. In this scenario, the combination of MSC and LL-37 may result in a robust combination to be clinically used. Methods: In the present study, the effects of LL-37 upon the proliferation and migratory capacity of human placenta-derived MSCs (pMSCs) were assessed by MTT and wound scratch assays. The influence of LL-37 over the immunosuppressive function of pMSCs was then investigated using CFSE cell division kit. Flow cytometry and real-time PCR were used to investigate the molecular mechanisms involved in the effects observed. Results: LL-37 had no detrimental effects over MSC proliferation and viability, as assessed by MTT assay. Moreover, the peptide promoted increased migratory behavior of pMSCs and enhanced their immunomodulatory function over activated human PBMCs. Strikingly, our data shows that LL-37 treatment leads to increased TLR3 levels, as shown by flow cytometry, and to an increased expression of factors classically related to immunosuppression, namely IDO, IL-10, TGF-β, IL-6, and IL-1β. Conclusions: Taken together, our observations may serve as groundwork for the development of new therapeutic strategies based on the combined use of LL-37 and MSCs, which may provide patients not only with an enhanced immunosuppression regime, but also with an agent to prevent opportunistic infections. 2017-07-24T15:27:13Z 2017-07-24T15:27:13Z 2016-12-30 Artigo BRAVO, Martha Oliveira et al. LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells. Stem Cell Research & Therapy, v. 7, Article 189, 30 dez. 2016. Disponível em: <https://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0448-3>. Acesso em: 19 jun. 2017. doi: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0448-3. http://repositorio.unb.br/handle/10482/23870 https://dx.doi.org/10.1186/s13287-016-0448-3 Inglês Acesso Aberto © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. application/pdf BioMed Central
institution	REPOSITORIO UNB
collection	REPOSITORIO UNB
language	Inglês
topic	Peptídeos Imunologia
spellingShingle	Peptídeos Imunologia Bravo, Martha Oliveira Sangiorgi, Bruno Braga Schiavinato, Josiane Lilian dos Santos Carvalho, Juliana Lott Covas, Dimas Tadeu Panepucci, Rodrigo Alexandre Neves, Francisco de Assis Rocha Franco, Octávio Luiz Pereira, Rinaldo Wellerson Araujo, Felipe Saldanha de LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells
description	Background: Although promising for graft-versus-host disease (GvHD) treatment, MSC therapy still faces important challenges. For instance, increasing MSC migratory capacity as well as potentializing immune response suppression are of interest. For GvHD management, preventing opportunistic infections is also a valuable strategy, since immunocompromised patients are easy targets for infections. LL-37 is a host defense peptide (HDP) that has been deeply investigated due to its immunomodulatory function. In this scenario, the combination of MSC and LL-37 may result in a robust combination to be clinically used. Methods: In the present study, the effects of LL-37 upon the proliferation and migratory capacity of human placenta-derived MSCs (pMSCs) were assessed by MTT and wound scratch assays. The influence of LL-37 over the immunosuppressive function of pMSCs was then investigated using CFSE cell division kit. Flow cytometry and real-time PCR were used to investigate the molecular mechanisms involved in the effects observed. Results: LL-37 had no detrimental effects over MSC proliferation and viability, as assessed by MTT assay. Moreover, the peptide promoted increased migratory behavior of pMSCs and enhanced their immunomodulatory function over activated human PBMCs. Strikingly, our data shows that LL-37 treatment leads to increased TLR3 levels, as shown by flow cytometry, and to an increased expression of factors classically related to immunosuppression, namely IDO, IL-10, TGF-β, IL-6, and IL-1β. Conclusions: Taken together, our observations may serve as groundwork for the development of new therapeutic strategies based on the combined use of LL-37 and MSCs, which may provide patients not only with an enhanced immunosuppression regime, but also with an agent to prevent opportunistic infections.
format	Artigo
author	Bravo, Martha Oliveira Sangiorgi, Bruno Braga Schiavinato, Josiane Lilian dos Santos Carvalho, Juliana Lott Covas, Dimas Tadeu Panepucci, Rodrigo Alexandre Neves, Francisco de Assis Rocha Franco, Octávio Luiz Pereira, Rinaldo Wellerson Araujo, Felipe Saldanha de
author_sort	Bravo, Martha Oliveira
title	LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells
title_short	LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells
title_full	LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells
title_fullStr	LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells
title_full_unstemmed	LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells
title_sort	ll-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells
publisher	BioMed Central
publishDate	2017
url	http://repositorio.unb.br/handle/10482/23870 https://dx.doi.org/10.1186/s13287-016-0448-3
_version_	1680624791098228736
score	13.657419

LL-37 boosts immunosuppressive function of placenta-derived mesenchymal stromal cells

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