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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| 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. |
| doi_str_mv | 10.1371/journal.pone.0031066 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0031066</identifier><identifier>PMID: 22328927</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal diseases ; Animal models ; Animals ; Antibodies ; Autoantibodies ; Autoantigens - immunology ; Biology ; Blister - drug therapy ; Blister - immunology ; Blistering ; Bullous pemphigoid ; Chromatography, Affinity ; Collagen ; Collagen Type XVII ; Complement C3 - metabolism ; Complement component C3 ; Dermatology ; Disease ; Enzyme-Linked Immunosorbent Assay ; Female ; Flavonoids ; Flow Cytometry ; Gene expression ; Granulocytes ; Granulocytes - drug effects ; Granulocytes - metabolism ; Immunization ; Immunoblotting ; Immunoglobulin G ; Immunoglobulin G - immunology ; Immunoglobulin G - pharmacology ; Immunoglobulins ; In vivo methods and tests ; Inflammation ; Leukocytes (granulocytic) ; Luteolin - therapeutic use ; Ly-6 antigen ; Matrix Metalloproteinase 9 - metabolism ; Medical treatment ; Medicine ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neonates ; Neutrophils ; Neutrophils - metabolism ; Non-Fibrillar Collagens - immunology ; Pemphigoid ; Pemphigoid, Bullous - chemically induced ; Pemphigoid, Bullous - drug therapy ; Pemphigoid, Bullous - immunology ; Proteins ; Rabbits ; Reactive Oxygen Species - metabolism ; Recruitment ; Respiratory burst ; Respiratory Burst - drug effects ; Rodents ; Separation ; Skin diseases ; Studies</subject><ispartof>PloS one, 2012-02, Vol.7 (2), p.e31066</ispartof><rights>2012 Oswald et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22328927</pmid><doi>10.1371/journal.pone.0031066</doi><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1323558833 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animal diseases Animal models Animals Antibodies Autoantibodies Autoantigens - immunology Biology Blister - drug therapy Blister - immunology Blistering Bullous pemphigoid Chromatography, Affinity Collagen Collagen Type XVII Complement C3 - metabolism Complement component C3 Dermatology Disease Enzyme-Linked Immunosorbent Assay Female Flavonoids Flow Cytometry Gene expression Granulocytes Granulocytes - drug effects Granulocytes - metabolism Immunization Immunoblotting Immunoglobulin G Immunoglobulin G - immunology Immunoglobulin G - pharmacology Immunoglobulins In vivo methods and tests Inflammation Leukocytes (granulocytic) Luteolin - therapeutic use Ly-6 antigen Matrix Metalloproteinase 9 - metabolism Medical treatment Medicine Mice Mice, Inbred BALB C Mice, Inbred C57BL Neonates Neutrophils Neutrophils - metabolism Non-Fibrillar Collagens - immunology Pemphigoid Pemphigoid, Bullous - chemically induced Pemphigoid, Bullous - drug therapy Pemphigoid, Bullous - immunology Proteins Rabbits Reactive Oxygen Species - metabolism Recruitment Respiratory burst Respiratory Burst - drug effects Rodents Separation Skin diseases Studies |
| title | The flavonoid luteolin inhibits Fcγ-dependent respiratory burst in granulocytes, but not skin blistering in a new model of pemphigoid in adult mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T21%3A39%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20flavonoid%20luteolin%20inhibits%20Fc%CE%B3-dependent%20respiratory%20burst%20in%20granulocytes,%20but%20not%20skin%20blistering%20in%20a%20new%20model%20of%20pemphigoid%20in%20adult%20mice&rft.jtitle=PloS%20one&rft.au=Oswald,%20Eva&rft.date=2012-02-06&rft.volume=7&rft.issue=2&rft.spage=e31066&rft.pages=e31066-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0031066&rft_dat=%3Cproquest_plos_%3E2936008341%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1323558833&rft_id=info:pmid/22328927&rft_doaj_id=oai_doaj_org_article_eb2938e3297044c8969a8f5fc46f6439&rfr_iscdi=true |