The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.

Bullous pemphigoid is an autoimmune blistering skin disease associated with autoantibodies against the dermal-epidermal junction. Passive transfer of antibodies against BP180/collagen (C) XVII, a major hemidesmosomal pemphigoid antigen, into neonatal mice results in dermal-epidermal separation upon...

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Autores principales:	Eva Oswald, Alina Sesarman, Claus-Werner Franzke, Ute Wölfle, Leena Bruckner-Tuderman, Thilo Jakob, Stefan F Martin, Cassian Sitaru
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eb2938e3297044c8969a8f5fc46f6439
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spelling	oai:doaj.org-article:eb2938e3297044c8969a8f5fc46f64392021-11-18T07:28:50ZThe flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.1932-620310.1371/journal.pone.0031066https://doaj.org/article/eb2938e3297044c8969a8f5fc46f64392012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22328927/?tool=EBIhttps://doaj.org/toc/1932-6203Bullous pemphigoid is an autoimmune blistering skin disease associated with autoantibodies against the dermal-epidermal junction. Passive transfer of antibodies against BP180/collagen (C) XVII, a major hemidesmosomal pemphigoid antigen, into neonatal mice results in dermal-epidermal separation upon applying gentle pressure to their skin, but not in spontaneous skin blistering. In addition, this neonatal mouse model precludes treatment and observation of diseased animals beyond 2-3 days. Therefore, in the present study we have developed a new disease model in mice reproducing the spontaneous blistering and the chronic course characteristic of the human condition. Adult mice were pre-immunized with rabbit IgG followed by injection of BP180/CXVII rabbit IgG. Mice pre-immunized against rabbit IgG and injected 6 times every second day with the BP180/CXVII-specific antibodies (n = 35) developed spontaneous sustained blistering of the skin, while mice pre-immunized and then treated with normal rabbit IgG (n = 5) did not. Blistering was associated with IgG and complement C3 deposits at the epidermal basement membrane and recruitment of inflammatory cells, and was partly dependent on Ly-6G-positive cells. We further used this new experimental model to investigate the therapeutic potential of luteolin, a plant flavonoid with potent anti-inflammatory and anti-oxidative properties and good safety profile, in experimental BP. Luteolin inhibited the Fcγ-dependent respiratory burst in immune complex-stimulated granulocytes and the autoantibody-induced dermal-epidermal separation in skin cryosections, but was not effective in suppressing the skin blistering in vivo. These studies establish a robust animal model that will be a useful tool for dissecting the mechanisms of blister formation and will facilitate the development of more effective therapeutic strategies for managing pemphigoid diseases.Eva OswaldAlina SesarmanClaus-Werner FranzkeUte WölfleLeena Bruckner-TudermanThilo JakobStefan F MartinCassian SitaruPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31066 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eva Oswald Alina Sesarman Claus-Werner Franzke Ute Wölfle Leena Bruckner-Tuderman Thilo Jakob Stefan F Martin Cassian Sitaru The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.
description	Bullous pemphigoid is an autoimmune blistering skin disease associated with autoantibodies against the dermal-epidermal junction. Passive transfer of antibodies against BP180/collagen (C) XVII, a major hemidesmosomal pemphigoid antigen, into neonatal mice results in dermal-epidermal separation upon applying gentle pressure to their skin, but not in spontaneous skin blistering. In addition, this neonatal mouse model precludes treatment and observation of diseased animals beyond 2-3 days. Therefore, in the present study we have developed a new disease model in mice reproducing the spontaneous blistering and the chronic course characteristic of the human condition. Adult mice were pre-immunized with rabbit IgG followed by injection of BP180/CXVII rabbit IgG. Mice pre-immunized against rabbit IgG and injected 6 times every second day with the BP180/CXVII-specific antibodies (n = 35) developed spontaneous sustained blistering of the skin, while mice pre-immunized and then treated with normal rabbit IgG (n = 5) did not. Blistering was associated with IgG and complement C3 deposits at the epidermal basement membrane and recruitment of inflammatory cells, and was partly dependent on Ly-6G-positive cells. We further used this new experimental model to investigate the therapeutic potential of luteolin, a plant flavonoid with potent anti-inflammatory and anti-oxidative properties and good safety profile, in experimental BP. Luteolin inhibited the Fcγ-dependent respiratory burst in immune complex-stimulated granulocytes and the autoantibody-induced dermal-epidermal separation in skin cryosections, but was not effective in suppressing the skin blistering in vivo. These studies establish a robust animal model that will be a useful tool for dissecting the mechanisms of blister formation and will facilitate the development of more effective therapeutic strategies for managing pemphigoid diseases.
format	article
author	Eva Oswald Alina Sesarman Claus-Werner Franzke Ute Wölfle Leena Bruckner-Tuderman Thilo Jakob Stefan F Martin Cassian Sitaru
author_facet	Eva Oswald Alina Sesarman Claus-Werner Franzke Ute Wölfle Leena Bruckner-Tuderman Thilo Jakob Stefan F Martin Cassian Sitaru
author_sort	Eva Oswald
title	The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.
title_short	The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.
title_full	The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.
title_fullStr	The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.
title_full_unstemmed	The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.
title_sort	flavonoid luteolin inhibits fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/eb2938e3297044c8969a8f5fc46f6439
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The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice.

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