{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:49:09Z","timestamp":1787500149389,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003286","name":"Kuwait Foundation for the Advancement of Sciences","doi-asserted-by":"publisher","award":["RA AH 2016-007"],"award-info":[{"award-number":["RA AH 2016-007"]}],"id":[{"id":"10.13039\/501100003286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>IP-10 (also called CXCL10) plays a significant role in leukocyte homing to inflamed tissues, and increased IP-10 levels are associated with the pathologies of various inflammatory disorders, including type 2 diabetes, atherosclerosis, and cancer. TNF-\u03b1 is a potent activator of immune cells and induces inflammatory cytokine expression in these cells. However, it is unclear whether TNF-\u03b1 is able to induce IP-10 expression in MCF-7 breast cancer cells. We therefore determined IP-10 expression in TNF-\u03b1-treated MCF-7 cells and investigated the mechanism involved. Our data show that TNF-\u03b1 induced\/upregulated the IP-10 expression at both mRNA and protein levels in MCF-7 cells. Inhibition of JNK (SP600125) significantly suppressed the TNF-\u03b1-induced IP-10 in MCF-7 cells, while the inhibition of p38 MAPK (SB203580), MEK1\/2 (U0126), and ERK1\/2 (PD98059) had no significant effect. Furthermore, TNF-\u03b1-induced IP-10 expression was abolished in MCF-7 cells deficient in JNK. Similar results were obtained using MCF-7 cells deficient in c-Jun. Moreover, the JNK kinase inhibitor markedly reduced the TNF-\u03b1-induced JNK and c-Jun phosphorylation. The kinase activity of JNK induced by TNF-\u03b1 stimulation of MCF-7 cells was significantly inhibited by SP600125. Altogether, our novel findings provide the evidence that TNF-\u03b1 induces IP-10 expression in MCF-7 breast cancer cells via activation of the JNK\/c-Jun signaling pathway.<\/jats:p>","DOI":"10.3390\/biom11091355","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T21:37:12Z","timestamp":1631569032000},"page":"1355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["TNF-\u03b1 Increases IP-10 Expression in MCF-7 Breast Cancer Cells via Activation of the JNK\/c-Jun Pathways"],"prefix":"10.3390","volume":"11","author":[{"given":"Shihab","family":"Kochumon","sequence":"first","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-0746","authenticated-orcid":false,"given":"Amnah","family":"Al-Sayyar","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Texy","family":"Jacob","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1793-7794","authenticated-orcid":false,"given":"Amal","family":"Hasan","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-3829","authenticated-orcid":false,"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[{"name":"Genetics & Bioinformatics Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9936-1575","authenticated-orcid":false,"given":"Sardar","family":"Sindhu","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"},{"name":"Animal and Imaging Core Facility, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5746-0743","authenticated-orcid":false,"given":"Rasheed","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Immunology & Microbiology Department, Dasman Diabetes Institute, Dasman 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cca.2021.07.011","article-title":"Breast cancer fibroblasts and cross-talk","volume":"521","author":"Magesh","year":"2021","journal-title":"Clin. 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