{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T20:02:29Z","timestamp":1784404949232,"version":"3.55.0"},"reference-count":68,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["109\u20102314\u2010B\u2010002\u2010181\u2010MY3"],"award-info":[{"award-number":["109\u20102314\u2010B\u2010002\u2010181\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112\u20102314\u2010B\u2010002\u2010229\u2010MY3"],"award-info":[{"award-number":["112\u20102314\u2010B\u2010002\u2010229\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["114\u20102314\u2010B\u2010002\u2010090"],"award-info":[{"award-number":["114\u20102314\u2010B\u2010002\u2010090"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["115\u2010S0197"],"award-info":[{"award-number":["115\u2010S0197"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006477","name":"National Taiwan University","doi-asserted-by":"publisher","award":["113L7246"],"award-info":[{"award-number":["113L7246"]}],"id":[{"id":"10.13039\/501100006477","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006477","name":"National Taiwan University","doi-asserted-by":"publisher","award":["114L7218"],"award-info":[{"award-number":["114L7218"]}],"id":[{"id":"10.13039\/501100006477","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with bronchitis and pulmonary emphysema phenotypes, with high morbidity and mortality. COPD is predicted to be the third leading cause of death by 2030. Periodontitis results from oral microbe dysbiosis, such as enrichment of periodontitis pathogens (e.g.,\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      ), which could disseminate to the lung via the blood stream or aspiration. Periodontitis pathogens are suggested to contribute to chronic inflammation and mucin secretion in the lung. Accordingly, periodontitis pathogens are associated with the pathogenesis and progression of COPD. However, clinical observation of a correlation between COPD and periodontitis is limited and the involved mechanism is not fully understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used a mouse model with ligature\u2010induced periodontitis and porcine pancreatic elastase (PPE)\u2010induced pulmonary emphysema to evaluate the roles of\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      and\n                      <jats:italic>Scardovia wiggsiae<\/jats:italic>\n                      in COPD progression. We analyzed proinflammatory cytokines, immune cells, apoptosis, and the extent of COPD progression using a multiplex assay\/enzyme\u2010linked immunosorbent assay, Hemacolor kit, terminal deoxynucleotidyl transferase nick\u2010end labeling assay, and the mean linear intercept and lung function, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results suggest that both oral bacterial species contributed to the periodontitis phenotype, promoted PPE\u2010induced proinflammatory cytokines in serum and bronchoalveolar lavage, and facilitated neutrophil infiltration in the lung. The abundance of neutrophils increased neutrophil elastase (NE) and downstream placenta growth factor (PGF) in the lung and led to alveolar epithelial cell apoptosis, pulmonary emphysema and lung function decline in the PPE\u2010treated mice. All pathological phenotype were attenuated by Ly6G antibody\u2010mediated neutrophil depletion in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrated a potential mechanism for periodontal\u2010associated progression to COPD via the neutrophil\u2010NE\u2010PGF pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>\n                      We demonstrated that the oral bacteria\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      and\n                      <jats:italic>Scardovia wiggsiae<\/jats:italic>\n                      exacerbate ligature\u2010induced inflammation and increase proinflammatory cytokines in local gingival crevicular fluid, systemic serum, and distal bronchoalveolar lavage, and are associated with more neutrophil infiltration in the lung. The in vivo experiment indicated that gingival infection with\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                      and\n                      <jats:italic>S. wiggsiae<\/jats:italic>\n                      worsens porcine pancreatic elastase\u2010induced pulmonary apoptosis and emphysema. Here, we show that\n                      <jats:italic>P. gingivalis and S. wiggsiae<\/jats:italic>\n                      are potential pathogenic factors for COPD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70091","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:32:46Z","timestamp":1771504366000},"page":"1516-1528","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Porphyromonas gingivalis<\/i>\n                    and\n                    <i>Scardovia wiggsiae<\/i>\n                    promote neutrophil\u2010induced lung epithelial cell apoptosis and emphysema"],"prefix":"10.1002","volume":"97","author":[{"given":"Hsin\u2010Han","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Dentistry National Taiwan University Hospital  Taipei Taiwan"},{"name":"Graduate Institute of Clinical Dentistry, School of Dentistry National Taiwan University  Taipei Taiwan"},{"name":"Graduate Institute of Oral Biology, School of Dentistry National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5818-0759","authenticated-orcid":false,"given":"Yen\u2010Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Taiwan University Hospital Yunlin Branch  Yunlin County Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine National Taiwan University  Taipei Taiwan"},{"name":"Thoracic Medicine Center, Department of Medicine and Surgery National Taiwan University Hospital Yunlin Branch  Yunlin County Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dentistry National Taiwan University Hospital  Taipei Taiwan"},{"name":"Graduate Institute of Clinical Dentistry, School of Dentistry National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-4129","authenticated-orcid":false,"given":"Chung\u2010Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Drug Hypersensitivity Clinical and Research Center Chang Gung Memorial Hospital  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4674-4892","authenticated-orcid":false,"given":"Shih\u2010Jung","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Dentistry National Taiwan University Hospital  Taipei Taiwan"},{"name":"Graduate Institute of Oral Biology, School of Dentistry National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Pin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Dentistry National Taiwan University Hospital  Taipei Taiwan"},{"name":"Graduate Institute of Clinical Dentistry, School of Dentistry National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Chien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Taiwan University Hospital, College of Medicine, National Taiwan University  Taipei Taiwan"},{"name":"Department of Internal Medicine National Taiwan University Cancer Center  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Ling","family":"Chu","sequence":"additional","affiliation":[{"name":"Second Degree Bachelor of Science in Nursing National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4729-6887","authenticated-orcid":false,"given":"Chong\u2010Jen","family":"Yu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine National Taiwan University  Taipei Taiwan"},{"name":"Department of Internal Medicine National Taiwan University Hospital, College of Medicine, National Taiwan University  Taipei Taiwan"},{"name":"Department of Internal Medicine National Taiwan University Hospital  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201204\u20100596PP"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.6077.1645"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(11)60968\u20109"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.4046\/trd.2023.0100"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0022\u20102018"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2006.060010"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00033"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S174898"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046508"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12247"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.17\u20100705"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010014\u20100104\u20103"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jebdp.2014.04.012"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047305"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.120399"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2017.1324725"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2004.75.1.9"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2001.72.1.50"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034519833630"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13228"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdsr.2021.10.003"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167-019-00163-4"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167\u2010019\u201000163\u20104"},{"issue":"1","key":"e_1_2_10_25_1","first-page":"15","article-title":"Biomaterials and biomechanics of oraland maxillofacial implants: current status and future developments","volume":"15","author":"Brunski JB","year":"2000","journal-title":"Int J Oral Maxillofac Implants"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.38"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1515\/folmed\u20102017\u20100080"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100757.2005.00113.x"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.01.146"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.49"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13077"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12867"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008578"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01168"},{"issue":"3","key":"e_1_2_10_35_1","first-page":"303","article-title":"Saliva between normal and pathological. Important factors in determining systemic and oral health","volume":"2","author":"Iorgulescu G","year":"2009","journal-title":"J Med Life"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201210\u20101913OC"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02006\u20102016"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02284\u201014"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/1348\u20100421.12157"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2014.11.001"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126527"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.126.5.1575"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1086\/593193"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000120"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9113433"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25173839"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211\u20105463.13066"},{"issue":"1","key":"e_1_2_10_48_1","first-page":"97","article-title":"Porphyromonas gingivalis induced inflammatory responses and promoted apoptosis in lung epithelial cells infected with H1N1 via the Bcl\u20112\/Bax\/Caspase\u20113 signaling pathway","volume":"18","author":"Chen Y","year":"2018","journal-title":"Mol Med Rep"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.8983"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12455"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13077"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010018\u20100035\u20104"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.21\u20100587"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.329"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.29190"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058\u2010016\u20100703\u20107"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01100.2009"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010014\u20100106\u20101"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2017.05.002"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.118.1.204"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2024.2334588"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S425172"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.2334\/josnusd.17\u20100357"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12091110"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.620681"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00197"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.03.016"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/958658"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00216.2017"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jper.70091","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jper.70091","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jper.70091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:17:27Z","timestamp":1784402247000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1002\/jper.70091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":68,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jper.70091"],"URL":"https:\/\/doi.org\/10.1002\/jper.70091","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"assertion":[{"value":"2024-11-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}