{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:14:55Z","timestamp":1792124095102,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,8]],"date-time":"2014-12-08T00:00:00Z","timestamp":1417996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Airway mucus hyperproduction is a common feature of chronic airway diseases such as severe asthma, chronic obstructive pulmonary disease and cystic fibrosis, which are closely associated with neutrophilic airway inflammation. S100A8, S100A9 and S100A12 are highly abundant proteins released by neutrophils and have been identified as important biomarkers in many inflammatory diseases. Herein, we report a new role for S100A8, S100A9 and S100A12 for producing MUC5AC, a major mucin protein in the respiratory tract. All three S100 proteins induced <jats:italic>MUC5AC <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and the protein in normal human bronchial epithelial cells as well as NCI\u2010H292 lung carcinoma cells in a dose\u2010dependent manner. A Toll\u2010like receptor 4 (TLR4) inhibitor almost completely abolished MUC5AC expression by all three S100 proteins, while neutralization of the receptor for advanced glycation end\u2010products (RAGE) inhibited only S100A12\u2010mediated production of MUC5AC. The S100 protein\u2010mediated production of MUC5AC was inhibited by the pharmacological agents that block prominent signalling molecules for MUC5AC expression, such as mitogen\u2010activated protein kinases, nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B (NF\u2010<jats:italic>\u03ba<\/jats:italic>B) and epidermal growth factor receptor. S100A8, S100A9 and S100A12 equally elicited both phosphorylation of extracellular signal\u2010regulated kinase (ERK) and nuclear translocation of NF\u2010<jats:italic>\u03ba<\/jats:italic>B\/degradation of cytosolic I<jats:italic>\u03ba<\/jats:italic>B with similar kinetics through TLR4. In contrast, S100A12 preferentially activated the ERK pathway rather than the NF\u2010<jats:italic>\u03ba<\/jats:italic>B pathway through RAGE. Collectively, these data reveal the capacity of these three S100 proteins to induce MUC5AC production in airway epithelial cells, suggesting that they all serve as key mediators linking neutrophil\u2010dominant airway inflammation to mucin hyperproduction.<\/jats:p>","DOI":"10.1111\/imm.12352","type":"journal-article","created":{"date-parts":[[2014,6,30]],"date-time":"2014-06-30T06:45:50Z","timestamp":1404110750000},"page":"79-90","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":158,"title":["S100A8, S100A9 and S100A12 activate airway epithelial cells to produce <scp>MUC<\/scp>5<scp>AC<\/scp> via extracellular signal\u2010regulated kinase and nuclear factor\u2010<i>\u03ba<\/i>B pathways"],"prefix":"10.1111","volume":"144","author":[{"given":"Jin Hyun","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Molecular and Life Sciences College of Science and Technology Hanyang University Ansan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae Mi","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Bionano Technology Hanyang University Ansan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il Yup","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Molecular and Life Sciences College of Science and Technology Hanyang University Ansan South Korea"},{"name":"Department of Bionano Technology Hanyang University Ansan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.5.9806170"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.3.9812110"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0492TR"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200304-505SO"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2009.03986.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-074942"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.13a35.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1999.276.5.L835"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.22.3.3768"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.2.2004039"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.70.113006.100441"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507977200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.09.157"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204862200"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300096200"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.09.059"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.6812"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306170"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)89506-4"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1638"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80801-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006993200"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1008647"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0607397"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.10.013"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2006.08.021"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2008.03186.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2013.06.028"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.5.2602"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003606"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2005.20.4.275"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401850"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0422"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1139\/Y09-054"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1939"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2012.03619.x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12139"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1009676"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.6.3233"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2520"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21639"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305790200"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-6-116"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800661"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318186262d"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.03.131"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.309"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2150"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22575"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000097"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1602OC"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.6.4009"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038629"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803732200"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12352","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12352","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T22:27:36Z","timestamp":1696458456000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,8]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1111\/imm.12352"],"URL":"https:\/\/doi.org\/10.1111\/imm.12352","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,8]]},"assertion":[{"value":"2014-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}