{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:38:55Z","timestamp":1770910735504,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2007,5,17]],"date-time":"2007-05-17T00:00:00Z","timestamp":1179360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background<\/jats:bold>The effects of protease\u2010activated receptor\u20102 (PAR\u20102) stimulation on inflammation mechanisms of chronic rhinosinusitis (CRS) are still unknown.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>PAR\u20102 receptor expression was investigated by immunohistochemistry and Taqman mRNA analysis in the mucosa of different rhinosinusitis entities. In primary nasal epithelial cell cultures, the function of PAR\u20102 and its ability to produce CXC, CC chemokines, and IL\u20106 were measured by calcium mobilization and stimulation tests. Inhibition tests were performed using cortisone, serine protease inhibitors, cysteine protease inhibitors, Pertussis toxin (PTX) and nuclear transcription factor (NF\u2010\u03baB) inhibition (BAY 11\u20107085). Signal transduction pathways were analysed by electromobility shift assays (EMSA) and NF\u2010\u03baB binding studies.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>The expression of PAR\u20102 was found to be increased in CRS specimens. The activation of PAR by trypsin or PAR\u20102\u2010specific activating peptide (AP) caused an increase in cytosolic calcium, as well as the release of the CXC chemokines IL\u20108 and growth\u2010related oncogene (GRO)\u2010\u03b1, but not the release of CC chemokines or IL\u20106. AP\u2010induced CXC chemokine was sensitive to PTX and activation of NF\u2010\u03baB was inhibited by BAY11\u20107085. Furthermore, a serine protease inhibitor significantly inhibited chemokine synthesis stimulated by trypsin and culture supernatants of staphylococci, whereas steroids and cysteine protease inhibitors had little effect.<\/jats:p><jats:p><jats:bold>Conclusion<\/jats:bold>PAR\u20102 plays a role in serine protease\u2010mediated regulation \u2013 staphylococcal and non\u2010staphylococcal origin \u2013 of IL\u20108 and GRO\u2010\u03b1 in nasal epithelial cells, but not in the regulation of CC chemokines. PAR\u20102 may therefore be involved in the pathophysiology of CRS and NP at different sites of activation, namely (i) proteases, (ii) the PAR\u20102 receptor itself or (iii) the application of novel agents that block NF\u2010\u03baB\/I\u03baB\u2010\u03b1 signalling.<\/jats:p>","DOI":"10.1111\/j.1365-2222.2007.02686.x","type":"journal-article","created":{"date-parts":[[2007,5,17]],"date-time":"2007-05-17T23:32:32Z","timestamp":1179444752000},"page":"1009-1022","source":"Crossref","is-referenced-by-count":44,"title":["PAR\u20102 activation regulates IL\u20108 and GRO\u2010\u03b1 synthesis by NF\u2010\u03baB, but not RANTES, IL\u20106, eotaxin or TARC expression in nasal epithelium"],"prefix":"10.1111","volume":"37","author":[{"given":"C.","family":"Rudack","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Steinhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Mooren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Buddenkotte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Von Eiff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Sachse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,5,17]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2005.00830.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.4065\/74.9.877"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-002-0027-9"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200565110-00006"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(97)80019-X"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2006.02501.x"},{"key":"e_1_2_6_8_2","first-page":"113","article-title":"Polypoid rhinosinusitis in patients with host defence deficiencies","volume":"35","author":"Rowe\u2010Jones JM","year":"1997","journal-title":"cellular infiltration and disease severity"},{"key":"e_1_2_6_9_2","first-page":"1","article-title":"Proteinase\u2010activated receptors","volume":"26","author":"Steinhoff M","year":"2005","journal-title":"transducers of proteinase-mediated signaling in inflammation and immune response"},{"key":"e_1_2_6_10_2","first-page":"t\u201052","article-title":"Proteinase\u2010activated receptors","volume":"274","author":"Dery O","year":"1998","journal-title":"novel mechanisms of signaling by serine proteases [Review] [167 refs]"},{"key":"e_1_2_6_11_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0031-6997(24)01493-5","article-title":"Proteinase\u2010activated receptors","volume":"53","author":"Macfarlane SR","year":"2001","journal-title":"Pharmacol Rev"},{"key":"e_1_2_6_12_2","first-page":"579","article-title":"Protease\u2010activated receptors","volume":"84","author":"Ossovskaya VS","year":"2004","journal-title":"contribution to physiology and disease"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.7.4043"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3220001"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01658.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2003.02390.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999003321455507"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999099313253"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21096"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0231OC"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0503221"},{"key":"e_1_2_6_22_2","first-page":"282","article-title":"Proteinase\u2010activated receptor\u20102 in human skin","volume":"8","author":"Steinhoff M","year":"1999","journal-title":"tissue distribution and activation of keratinocytes by mast cell tryptase"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.23539.x"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00098.2005"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.1014"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.08.050"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2006.02537.x"},{"key":"e_1_2_6_28_2","first-page":"797","article-title":"Protease\u2010activated receptors in human airways","volume":"108","author":"Knight DA","year":"2001","journal-title":"upregulation of PAR-2 in respiratory epithelium from patients with asthma"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.22415.x"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.278.1.L193"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/pupt.2001.0285"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.25.14910"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/18223"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1086\/315027"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2000.106210"},{"key":"e_1_2_6_36_2","first-page":"23","article-title":"The CXC chemokine GCP\u20102\/CXCL6 is predominantly induced in mesenchymal cells by interleukin\u20101beta and is down\u2010regulated by interferon\u2010gamma","volume":"83","author":"Wuyts A","year":"2003","journal-title":"comparison with interleukin-8\/CXCL8"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00762.x"},{"key":"e_1_2_6_38_2","first-page":"1992","article-title":"CXCR1\u2010binding chemokines in inflammatory bowel diseases","volume":"34","author":"Gijsbers K","year":"2004","journal-title":"down-regulated IL-8\/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2\/CXCL6 expression in inflamed intestinal tissue"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1078\/1438-4221-00112"},{"key":"e_1_2_6_40_2","first-page":"995","article-title":"Selected contribution","volume":"91","author":"Berger P","year":"2001","journal-title":"tryptase-induced PAR-2-mediated Ca(2+) signaling in human airway smooth muscle cells"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007020170083"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000033520.95242.A2"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.36.22003"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.11.7191"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.7.1914"},{"key":"e_1_2_6_46_2","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.4049\/jimmunol.156.10.3961","article-title":"Salicylates inhibit I kappa B\u2010alpha phosphorylation, endothelial\u2010 leukocyte adhesion molecule expression, and neutrophil transmigration","volume":"156","author":"Pierce JW","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8052854"},{"key":"e_1_2_6_48_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118074"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2004-0161OC"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2222.2007.02686.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2222.2007.02686.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T11:57:23Z","timestamp":1737028643000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2222.2007.02686.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,17]]},"references-count":48,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2007,7]]}},"alternative-id":["10.1111\/j.1365-2222.2007.02686.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2222.2007.02686.x","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,17]]}}}