{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:00:46Z","timestamp":1791658846677,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE15566"],"award-info":[{"award-number":["DE15566"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DE19938"],"award-info":[{"award-number":["DE19938"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Chronic periodontitis (CP) is an inflammatory disease in which cytokines play a major role in the progression of disease. Anti\u2010inflammatory cytokines (interleukin 4 [IL\u20104] and IL\u201010) were reported to be absent or reduced in diseased periodontal tissues, suggesting an imbalance between the proinflammatory and anti\u2010inflammatory mediators. This study tests the hypothesis that there is cellular crosstalk mediated by proinflammatory and anti\u2010inflammatory cytokines and that blocking proinflammatory cytokine (tumor necrosis factor\u2010\u03b1 [TNF\u2010\u03b1] and IL\u20101) production will enhance anti\u2010inflammatory cytokine (IL\u20104 and IL\u201010) production from peripheral blood mononuclear cells (PBMCs) in response to <jats:italic>Porphyromonas gingivalis<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> PBMCs were isolated from individuals diagnosed with CP or healthy individuals and cultured for 24 hours. Concanavalin A (ConA) was used as an activator of lymphocyte function. Live and heat\u2010killed <jats:italic>P. gingivalis<\/jats:italic> or lipopolysaccharide from <jats:italic>P. gingivalis<\/jats:italic> were used as the bacterial stimulants. TNF\u2010\u03b1 and IL\u20101 production was neutralized by specific antibodies against TNF\u2010\u03b1 and IL\u20101\u03b1 or IL\u2010\u03b2. Culture supernatants were evaluated by enzyme\u2010linked immunosorbent assay for TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20104, and IL\u201010 production.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Live <jats:italic>P. gingivalis<\/jats:italic> did not result in any significant IL\u201010 or IL\u20104 release, whereas heat\u2010killed <jats:italic>P. gingivalis<\/jats:italic> led to a significant increase in IL\u201010 levels compared with unstimulated or live <jats:italic>P. gingivalis<\/jats:italic>\u2013stimulated cells from both healthy individuals or those with CP. Overall, PBMCs from patients with CP produced significantly lower IL\u201010 in response to ConA and <jats:italic>P. gingivalis<\/jats:italic>, suggesting chronic suppression of the anti\u2010inflammatory cytokine production. Blocking the proinflammatory cytokine response did not result in any substantial change in IL\u201010 or IL\u20104 response to live <jats:italic>P. gingivalis<\/jats:italic>. Blocking the proinflammatory cytokine response restored IL\u201010 production by cells from CP in response to <jats:italic>P. gingivalis<\/jats:italic> lipopolysaccharide.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> These findings suggest that PBMCs from patients with CP have suppressed anti\u2010inflammatory cytokine production that can, in part, be restored by neutralizing proinflammatory cytokines. Monocytes are an important source of IL\u201010 production, and monocyte\u2010derived IL\u201010 might play a regulatory role in the pathogenesis of CP.<\/jats:p>","DOI":"10.1902\/jop.2012.120422","type":"journal-article","created":{"date-parts":[[2012,11,23]],"date-time":"2012-11-23T08:23:25Z","timestamp":1353659005000},"page":"1337-1345","source":"Crossref","is-referenced-by-count":15,"title":["Blocking Proinflammatory Cytokine Release Modulates Peripheral Blood Mononuclear Cell Response to <i>Porphyromonas gingivalis<\/i>"],"prefix":"10.1002","volume":"84","author":[{"given":"Ezel","family":"Berker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alpdogan","family":"Kantarci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Hasturk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Van Dyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945011794815310"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016350902841890"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2009.01225.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/154411130201300204"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.1997.tb00191.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2007.07.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608500301"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910208100503"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2007.01079.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00600-10"},{"key":"e_1_2_7_12_1","first-page":"2348","article-title":"Two types of helper T cells clones","volume":"136","author":"Mossman TR","year":"1986","journal-title":"J Immunol"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.117.4.1162"},{"key":"e_1_2_7_14_1","first-page":"1239","article-title":"Gingival mononuclear cells from chronic inflammatory periodontal tissues produce interleukin (IL)\u20105 and IL\u20106 but not IL\u20102 and IL\u20104","volume":"142","author":"Fujihashi K","year":"1993","journal-title":"Am J Pathol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.1995.tb00159.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9969(99)00094-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2000.71.11.1756"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390318"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2012.42.1.3"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2005.76.11-S.2066"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.5.1517"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390516"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.1999.4.1.1"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.4.1255-1263.1991"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.393-401.1995"},{"key":"e_1_2_7_26_1","first-page":"83","article-title":"Bacterial lipopolysaccharide. 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