{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:32:28Z","timestamp":1791318748174,"version":"4.3.1"},"reference-count":71,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,1,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Asthma is a chronic inflammatory disease of the airways characterized by recurrent episodes of airway obstruction, hyperresponsiveness, remodeling, and eosinophilia. Phospholipase A\n                    <jats:sub>2<\/jats:sub>\n                    s (PLA\n                    <jats:sub>2<\/jats:sub>\n                    s), which release fatty acids and lysophospholipids from membrane phospholipids, have been implicated in exacerbating asthma by generating pro\u2010asthmatic lipid mediators, but an understanding of the association between individual PLA\n                    <jats:sub>2<\/jats:sub>\n                    subtypes and asthma is still incomplete. Here, we show that group III\u2010secreted PLA\n                    <jats:sub>2<\/jats:sub>\n                    (sPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u2010III) plays an ameliorating, rather than aggravating, role in asthma pathology. In both mouse and human lungs, sPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u2010III was expressed in bronchial epithelial cells and decreased during the asthmatic response. In an ovalbumin (OVA)\u2010induced asthma model,\n                    <jats:italic>Pla2g3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice exhibited enhanced airway hyperresponsiveness, eosinophilia, OVA\u2010specific IgE production, and type 2 cytokine expression as compared to\n                    <jats:italic>Pla2g3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Lipidomics analysis showed that the pulmonary levels of several lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidic acid (LPA), were decreased in OVA\u2010challenged\n                    <jats:italic>Pla2g3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice relative to\n                    <jats:italic>Pla2g3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice. LPA receptor 2 (LPA\n                    <jats:sub>2<\/jats:sub>\n                    ) agonists suppressed thymic stromal lymphopoietin (TSLP) expression in bronchial epithelial cells and reversed airway hyperresponsiveness and eosinophilia in\n                    <jats:italic>Pla2g3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, suggesting that sPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u2010III negatively regulates allergen\u2010induced asthma at least by producing LPA. Thus, the activation of the sPLA\n                    <jats:sub>2<\/jats:sub>\n                    \u2010III\u2010LPA pathway may be a new therapeutic target for allergic asthma.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301976r","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T10:19:28Z","timestamp":1705573168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Group\n                    <scp>III<\/scp>\n                    secreted phospholipase\n                    <scp>\n                      A\n                      <sub>2<\/sub>\n                    <\/scp>\n                    \u2010driven lysophospholipid pathway protects against allergic asthma"],"prefix":"10.1096","volume":"38","author":[{"given":"Asako","family":"Hamu\u2010Tanoue","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences 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