{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:37:22Z","timestamp":1784939842547,"version":"3.55.0"},"reference-count":15,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T00:00:00Z","timestamp":1172707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Rhinology"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recruitment of macrophages is crucial to the pathogenesis of the nasal polyp (NP) because this disease is believed to be inflammation related. Information regarding the expression of C-C chemokine ligand 2 (CCL2), an essential modulator of monocyte chemotaxis in nasal polyp fibroblasts (NPFs), remains unavailable. In this study, the effects of tumor necrosis factor (TNF)-\u03b1 on CCL2 expression in NPFs and the signaling pathway involved were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary cultures of NPFs were established from NPs. The expressions of CCL2, c-Fos, and c-Jun mRNAs in NPF after TNF-\u03b1 stimulation were detected by Northern blot. Western blot was used to examine the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Activator protein (AP) 1\/DNA interactions were evaluated by electrophoretic mobility shift assay (EMSA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Northern blot showed that TNF-\u03b1 stimulated CCL2 gene expression in NPFs. Significant increase of B-Raf, phosphorated MAPK including mitogen-activated ERK-activate kinase (MEK)1\/2, extracellular signal-related kinase 1\/2, and p38 were detected by Western blot. c-Fos and c-Jun mRNAs were induced by TNF-\u03b1, and PD98059 (MEK inhibitor) and SB203580 (p38 inhibitor) abolished the up-regulation of c-Fos. EMSA revealed that TNF-\u03b1 increased AP-1\/DNA binding, and PD98059 and SB203580 attenuated this reaction, possibly via reducing c-Fos synthesis. PD98059 and curcumin (AP-1 inhibitor) markedly suppressed the TNF-\u03b1\u2013induced CCL2 expression, whereas the effect of SB203580 was less noted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TNF-\u03b1 induces CCL2 transcription in NPFs. B-Raf\/MEK\/ERK signaling cascade and to a less extent the p38 pathway are responsible for c-Fos activation and the subsequent AP-1\/DNA interaction leading to CCL2 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2500\/ajr.2007.21.2958","type":"journal-article","created":{"date-parts":[[2007,3,28]],"date-time":"2007-03-28T19:25:54Z","timestamp":1175109954000},"page":"251-255","source":"Crossref","is-referenced-by-count":25,"title":["Tumor Necrosis Factor-\u03b1 Stimulates the Expression of C-C Chemokine Ligand 2 Gene in Fibroblasts from the Human Nasal Polyp through the Pathways of Mitogen-Activated Protein Kinase"],"prefix":"10.1177","volume":"21","author":[{"given":"Sze-Kwan","family":"Lin","sequence":"first","affiliation":[{"name":"Departments of Dentistry, National Taiwan University Hospital, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Heng","family":"Kok","sequence":"additional","affiliation":[{"name":"Departments of Dentistry, National Taiwan University Hospital, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Tung","family":"Shun","sequence":"additional","affiliation":[{"name":"Departments of Forensic Medicine, National Taiwan University Hospital, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Yuan","family":"Hong","sequence":"additional","affiliation":[{"name":"Departments of Dentistry, National Taiwan University Hospital, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Che","family":"Hsu","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology, National Taiwan University Hospital, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology, National Taiwan University Hospital, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2007,3,1]]},"reference":[{"key":"bibr1-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1177\/000348940511401112"},{"key":"bibr2-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.153.5.2278"},{"key":"bibr3-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200007000-00022"},{"key":"bibr4-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1177\/000348940111001209"},{"key":"bibr5-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.128.8.945"},{"key":"bibr6-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.09.040191.003153"},{"key":"bibr7-ajr.2007.21.2958","first-page":"1711","volume":"150","author":"Volejnikova S.","year":"1997","journal-title":"Am J Pathol"},{"key":"bibr8-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1016\/1357-4310(96)88772-7"},{"key":"bibr9-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1038\/35065000"},{"key":"bibr10-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(97)80068-3"},{"key":"bibr11-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.807"},{"key":"bibr12-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5292"},{"key":"bibr13-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.3109\/00016489609137920"},{"key":"bibr14-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1038\/24884"},{"key":"bibr15-ajr.2007.21.2958","doi-asserted-by":"publisher","DOI":"10.1042\/bj3510289"}],"container-title":["American Journal of Rhinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.2500\/ajr.2007.21.2958","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.2500\/ajr.2007.21.2958","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:36:31Z","timestamp":1777368991000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.2500\/ajr.2007.21.2958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,3]]}},"alternative-id":["10.2500\/ajr.2007.21.2958"],"URL":"https:\/\/doi.org\/10.2500\/ajr.2007.21.2958","relation":{},"ISSN":["1050-6586","1539-6290"],"issn-type":[{"value":"1050-6586","type":"print"},{"value":"1539-6290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3]]}}}