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The virulence of<jats:named-content content-type=\"genus-species\">P. gingivalis<\/jats:named-content>likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated (<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1690<\/jats:sub>) to the tetra-acylated (<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1435\/1449<\/jats:sub>) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human \u03b2-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2).<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1690<\/jats:sub>caused substantial inhibition of HDP-induced mast cell degranulation, but<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1435\/1449<\/jats:sub>had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1690<\/jats:sub>inhibited this binding, but<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1435\/1449<\/jats:sub>had no effect. These findings suggest that low-level inflammation induced by HDP\/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1690<\/jats:sub>and<jats:italic>Pg<\/jats:italic>LPS<jats:sub>1435\/1449<\/jats:sub>may contribute to the modulation of disease progression.<\/jats:p>","DOI":"10.1128\/iai.00246-17","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:20:11Z","timestamp":1499732411000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide"],"prefix":"10.1128","volume":"85","author":[{"given":"Kshitij","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chizobam","family":"Idahosa","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saptarshi","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donguk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hariharan","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuradha","family":"Dhingra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Boesze-Battaglia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Korostoff","sequence":"additional","affiliation":[{"name":"Department of Periodontics, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hydar","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2337"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512453589"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.09.001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344202"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.4.1660-1665.1998"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000697"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2014.999567"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2009.03.009"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01924-05"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00900-10"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058496"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.9.5041-5051.2004"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep29829"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00859.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004215"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240248"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2009.00333.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2010.00350.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80010-7"},{"key":"e_1_3_2_21_2","first-page":"225","article-title":"Mast cells initiate early anti-Listeria host defences","volume":"10","author":"Gekara NO","year":"2008","unstructured":"Gekara NO Weiss S . 2008. 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