Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice

Abstract The mechanism underlying bee venom (BV) therapy is still controversial, with opinions ranging from constituent-based pharmacological action to homeopathic-like activity. The purpose of this study was to examine whether BV phospholipase A2 (bvPLA2), an enzymatic component of BV, is a novel a...

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Autores principales:	Gwang-Muk Choi, Bombi Lee, Riwon Hong, Seon-Young Park, Da-Eun Cho, Mijung Yeom, Hi-Joon Park, Hyunsu Bae, Dae-Hyun Hahm
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eb59a42cc7054f51a6a85a1f7637c4f5
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spelling	oai:doaj.org-article:eb59a42cc7054f51a6a85a1f7637c4f52021-12-02T14:11:31ZBee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice10.1038/s41598-021-82298-x2045-2322https://doaj.org/article/eb59a42cc7054f51a6a85a1f7637c4f52021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82298-xhttps://doaj.org/toc/2045-2322Abstract The mechanism underlying bee venom (BV) therapy is still controversial, with opinions ranging from constituent-based pharmacological action to homeopathic-like activity. The purpose of this study was to examine whether BV phospholipase A2 (bvPLA2), an enzymatic component of BV, is a novel anti-inflammatory and anti-arthritic mediator capable of stimulating CD25+ Foxp3+ regulatory T cell (Treg) polarization in a mouse model of human rheumatoid arthritis (RA). An experimental model of RA was established in male DBA/1 mouse by 2-week-interval injections of 100 μg type II collagen emulsified in complete (first injection) or incomplete Freund’s adjuvant (second injection) at the base of the tail. During arthritis development, bvPLA2 (0.1, 0.5, 1.0 mg/kg) and/or Treg inhibitors such as anti-CD25 antibodies and peptide 60 (P60) were injected intraperitoneally for 5 weeks. Arthritic symptoms and the expansion of Tregs were then assessed by behavioral assessments, histological and micro-CT imaging, and flow cytometry. bvPLA2 injections significantly alleviated arthritic behaviors such as squeaking and joint swelling, consistent with changes seen on both histological and micro-CT images. The anti-arthritic effects of bvPLA2 were blocked by intraperitoneal injections of 0.25 mg/kg anti-CD25 antibody and 10 μg/kg P60, as determined by behavioral assessments. Flow cytometric analysis of dendritic cells, B cells, and major T cell subsets from spleens revealed a significant depletion of Tregs following anti-CD25 antibody, but not P60, treatment. bvPLA2 treatment exerted significant anti-inflammatory and anti-arthritic activities in a mouse model of RA via the induction of Tregs.Gwang-Muk ChoiBombi LeeRiwon HongSeon-Young ParkDa-Eun ChoMijung YeomHi-Joon ParkHyunsu BaeDae-Hyun HahmNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gwang-Muk Choi Bombi Lee Riwon Hong Seon-Young Park Da-Eun Cho Mijung Yeom Hi-Joon Park Hyunsu Bae Dae-Hyun Hahm Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice
description	Abstract The mechanism underlying bee venom (BV) therapy is still controversial, with opinions ranging from constituent-based pharmacological action to homeopathic-like activity. The purpose of this study was to examine whether BV phospholipase A2 (bvPLA2), an enzymatic component of BV, is a novel anti-inflammatory and anti-arthritic mediator capable of stimulating CD25+ Foxp3+ regulatory T cell (Treg) polarization in a mouse model of human rheumatoid arthritis (RA). An experimental model of RA was established in male DBA/1 mouse by 2-week-interval injections of 100 μg type II collagen emulsified in complete (first injection) or incomplete Freund’s adjuvant (second injection) at the base of the tail. During arthritis development, bvPLA2 (0.1, 0.5, 1.0 mg/kg) and/or Treg inhibitors such as anti-CD25 antibodies and peptide 60 (P60) were injected intraperitoneally for 5 weeks. Arthritic symptoms and the expansion of Tregs were then assessed by behavioral assessments, histological and micro-CT imaging, and flow cytometry. bvPLA2 injections significantly alleviated arthritic behaviors such as squeaking and joint swelling, consistent with changes seen on both histological and micro-CT images. The anti-arthritic effects of bvPLA2 were blocked by intraperitoneal injections of 0.25 mg/kg anti-CD25 antibody and 10 μg/kg P60, as determined by behavioral assessments. Flow cytometric analysis of dendritic cells, B cells, and major T cell subsets from spleens revealed a significant depletion of Tregs following anti-CD25 antibody, but not P60, treatment. bvPLA2 treatment exerted significant anti-inflammatory and anti-arthritic activities in a mouse model of RA via the induction of Tregs.
format	article
author	Gwang-Muk Choi Bombi Lee Riwon Hong Seon-Young Park Da-Eun Cho Mijung Yeom Hi-Joon Park Hyunsu Bae Dae-Hyun Hahm
author_facet	Gwang-Muk Choi Bombi Lee Riwon Hong Seon-Young Park Da-Eun Cho Mijung Yeom Hi-Joon Park Hyunsu Bae Dae-Hyun Hahm
author_sort	Gwang-Muk Choi
title	Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice
title_short	Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice
title_full	Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice
title_fullStr	Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice
title_full_unstemmed	Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice
title_sort	bee venom phospholipase a2 alleviates collagen-induced polyarthritis by inducing foxp3+ regulatory t cell polarization in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eb59a42cc7054f51a6a85a1f7637c4f5
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Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3+ regulatory T cell polarization in mice

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