{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T12:15:45Z","timestamp":1768738545545,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2017,2,18]],"date-time":"2017-02-18T00:00:00Z","timestamp":1487376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2013-068954"],"award-info":[{"award-number":["2013-068954"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1\/Th2 cytokines were elevated in DFE\/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.<\/jats:p>","DOI":"10.3390\/toxins9020068","type":"journal-article","created":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T11:07:24Z","timestamp":1487588844000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Kyung-Hwa","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunjung","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manho","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namsik","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Korean Medicine, Graduate School, Kyung Hee Univeristy, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0299-3582","authenticated-orcid":false,"given":"Hyunsu","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,2,18]]},"reference":[{"key":"ref_1","first-page":"35","article-title":"Atopic dermatitis: An overview","volume":"86","author":"Berke","year":"2012","journal-title":"Am. Fam. Physician"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1067\/mai.2000.106484","article-title":"Atopic dermatitis: New insights and opportunities for therapeutic intervention","volume":"105","author":"Leung","year":"2000","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1172\/JCI21060","article-title":"New insights into atopic dermatitis","volume":"113","author":"Leung","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.4049\/jimmunol.174.6.3695","article-title":"IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes","volume":"174","author":"Boniface","year":"2005","journal-title":"J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/ng1767","article-title":"Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis","volume":"38","author":"Palmer","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/j.1398-9995.2006.01153.x","article-title":"Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology\/American Academy of Allergy, Asthma and Immunology\/PRACTALL Consensus Report","volume":"61","author":"Akdis","year":"2006","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1398-9995.2008.01922.x","article-title":"New insights into the mechanism and management of allergic diseases: Atopic dermatitis","volume":"64","author":"Novak","year":"2009","journal-title":"Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1067\/mjd.2002.124617","article-title":"Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: Changes in barrier function provide a sensitive indicator of disease activity","volume":"47","author":"Chamlin","year":"2002","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1126\/science.177.4046.314","article-title":"Bee and wasp venoms","volume":"177","author":"Habermann","year":"1972","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0091-6749(76)90076-2","article-title":"Allergy to insect stings. II. Phospholipase A: The major allergen in honeybee venom","volume":"57","author":"Sobotka","year":"1976","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10540-006-9030-z","article-title":"Melittin: A membrane-active peptide with diverse functions","volume":"27","author":"Raghuraman","year":"2007","journal-title":"Biosci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1179\/016164109X12537002794282","article-title":"Neuroprotective effects of bee venom pharmaceutical acupuncture in acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson\u2019s disease","volume":"32","author":"Doo","year":"2010","journal-title":"Neurol. Res."},{"key":"ref_13","first-page":"470","article-title":"A phase I study of the safety of honeybee venom extract as a possible treatment for patients with progressive forms of multiple sclerosis","volume":"26","author":"Castro","year":"2005","journal-title":"Allergy Asthma Proc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.pneurobio.2010.06.006","article-title":"The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword","volume":"92","author":"Chen","year":"2010","journal-title":"Prog. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1096\/fasebj.5.7.1901288","article-title":"Role of phospholipase in generating lipid second messengers in signal transduction","volume":"5","author":"Dennis","year":"1991","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0006-2952(94)90216-X","article-title":"Phospholipase A2 enzymes: Regulation and physiological role","volume":"48","author":"Mukherjee","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/ki.2015.147","article-title":"Phospholipase A2 inhibits cisplatin-induced acute kidney injury by modulating regulatory T cells by the CD206 mannose receptor","volume":"88","author":"Kim","year":"2015","journal-title":"Kidney Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/iid3.76","article-title":"Bee venom phospholipase A2 suppresses allergic airway inflammation in an ovalbumin-induced asthma model through the induction of regulatory T cells","volume":"3","author":"Park","year":"2015","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.4049\/jimmunol.172.6.3822","article-title":"Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses","volume":"172","author":"Angeli","year":"2004","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.intimp.2011.04.005","article-title":"DA-9601 suppresses 2,4-dinitrochlorobenzene and dust mite extract-induced atopic dermatitis-like skin lesions","volume":"11","author":"Choi","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.coi.2009.09.006","article-title":"Mast cells in atopic dermatitis","volume":"21","author":"Kawakami","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"ref_22","first-page":"55S","article-title":"T regulatory cells in allergy","volume":"24","author":"Braga","year":"2011","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1046\/j.1365-2222.2003.01749.x","article-title":"Family history and risk of atopic dermatitis in children up to 4 years","volume":"33","author":"Bohme","year":"2003","journal-title":"Clin. Exp. Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1097\/00008480-200210000-00012","article-title":"Atopic diseases of childhood","volume":"14","author":"Stone","year":"2002","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S560","DOI":"10.1067\/mai.2003.78","article-title":"11. Allergic and immunologic diseases of the skin","volume":"111","author":"Blauvelt","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.jaci.2012.07.012","article-title":"Progressive activation of T(H)2\/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis","volume":"130","author":"Gittler","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0952-7915(01)00287-4","article-title":"T-cell subpopulations in the development of atopic and contact allergy","volume":"13","author":"Girolomoni","year":"2001","journal-title":"Curr. Opin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jep.2016.08.004","article-title":"Water soluble extracts from Actinidia arguta, PG102, attenuates house dust mite-induced murine atopic dermatitis by inhibiting the mTOR pathway with Treg generation","volume":"193","author":"Bae","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.jaci.2005.08.046","article-title":"Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice","volume":"116","author":"Lin","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1136\/jmedgenet-2012-100759","article-title":"The immunogenetics of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome","volume":"49","author":"Torgerson","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.4049\/jimmunol.1500386","article-title":"Bee Venom Phospholipase A2, a Novel Foxp3+ Regulatory T Cell Inducer, Protects Dopaminergic Neurons by Modulating Neuroinflammatory Responses in a Mouse Model of Parkinson\u2019s Disease","volume":"195","author":"Chung","year":"2015","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1177\/1535370213477975","article-title":"Rutin suppresses atopic dermatitis and allergic contact dermatitis","volume":"238","author":"Choi","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/intimm\/9.3.461","article-title":"Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC\/Nga mice","volume":"9","author":"Matsuda","year":"1997","journal-title":"Int. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jep.2007.11.042","article-title":"The bark of Betula platyphylla var. japonica inhibits the development of atopic dermatitis-like skin lesions in NC\/Nga mice","volume":"116","author":"Kim","year":"2008","journal-title":"J. Ethnopharmacol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/2\/68\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:28:37Z","timestamp":1760207317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/2\/68"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,18]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,2]]}},"alternative-id":["toxins9020068"],"URL":"https:\/\/doi.org\/10.3390\/toxins9020068","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,18]]}}}