{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:39:24Z","timestamp":1792276764455,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["RTA5780012"],"award-info":[{"award-number":["RTA5780012"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["RSA6180068"],"award-info":[{"award-number":["RSA6180068"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholangiocarcinoma (CCA), an aggressive cancer of bile ducts, is a well-known chronic inflammation-related disease. The major impediment in CCA treatment is limited treatment options for advanced disease; hence, an alternative is urgently required. The role of CD147 on cytokine production has been observed in inflammation-related diseases, but not in CCA. Therefore, this study was focused on CD147-promoting proinflammatory cytokine production and functions. Proinflammatory cytokine profiles were compared between CD147 expressing CCA cells and CD147 knockout cells (CD147 KO). Three cytokines, namely interleukin (IL)-6, IL-8, and granulocyte\u2013monocyte colony-stimulating factor (GM-CSF), were dramatically diminished in CD147 KO clones. The involvement of the CD147-related cytokines in CCA invasion was established. CD147-promoted IL-6, IL-8, and GM-CSF secretions were regulated by NF-\u03baB nuclear translocation, Akt activation, and p38 phosphorylation. CD147-fostering IL-6 production was dependent on soluble CD147, CD147 homophilic interaction, and NF-\u03baB function. The overexpression of specific genes in CCA tissues compared to normal counterparts emphasized the clinical importance of these molecules. Altogether, CD147-potentiated proinflammatory cytokine production leading to CCA cell invasion is shown for the first time in the current study. This suggests that modulation of CD147-related inflammation might be a promising choice for advanced CCA treatment.<\/jats:p>","DOI":"10.3390\/ijms222413496","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T11:27:36Z","timestamp":1639654056000},"page":"13496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Homophilic Interaction of CD147 Promotes IL-6-Mediated Cholangiocarcinoma Invasion via the NF-\u03baB-Dependent Pathway"],"prefix":"10.3390","volume":"22","author":[{"given":"Paweena","family":"Dana","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusho","family":"Kariya","sequence":"additional","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-0169","authenticated-orcid":false,"given":"Worachart","family":"Lert-itthiporn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wunchana","family":"Seubwai","sequence":"additional","affiliation":[{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saowaluk","family":"Saisomboon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-211X","authenticated-orcid":false,"given":"Chaisiri","family":"Wongkham","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-5206","authenticated-orcid":false,"given":"Seiji","family":"Okada","sequence":"additional","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9578-3041","authenticated-orcid":false,"given":"Sopit","family":"Wongkham","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-9680","authenticated-orcid":false,"given":"Kulthida","family":"Vaeteewoottacharn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/MOG.0b013e3282fbf9b3","article-title":"Cholangiocarcinoma: Lessons from Thailand","volume":"24","author":"Sripa","year":"2008","journal-title":"Curr. 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