TLR4/NF-κB axis induces fludarabine resistance by suppressing TXNIP expression in acute myeloid leukemia cells

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dc.contributor.authorH Huy-
dc.contributor.authorTae-Don Kim-
dc.contributor.authorWon Sam Kim-
dc.contributor.authorDong Oh Kim-
dc.contributor.authorJae-Eun Byun-
dc.contributor.authorMi Jeong Kim-
dc.contributor.authorYoung-Jun Park-
dc.contributor.authorSuk Ran Yoon-
dc.contributor.authorJi Yoon Noh-
dc.contributor.authorJung Woon Lee-
dc.contributor.authorK H Lee-
dc.contributor.authorIn Pyo Choi-
dc.contributor.authorHaiyoung Jung-
dc.date.accessioned2019-01-23T16:30:34Z-
dc.date.available2019-01-23T16:30:34Z-
dc.date.issued2018-
dc.identifier.issn0006-291X-
dc.identifier.uri10.1016/j.bbrc.2018.10.047ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/18178-
dc.description.abstractOvercoming drug resistance is one of key issues in treating refractory acute myeloid leukemia (AML). The Toll-like receptor 4 (TLR4) signaling pathway is involved in many aspects of biological functions of AML cells, including the regulation of pro-inflammatory cytokine products, myeloid differentiation, and survival of AML cells. Thus, targeting TLR4 of AML patients for therapeutic purposes should be carefully addressed. In this regard, we investigated the possible role of TLR4 as a regulatory factor against fludarabine (FA) cytotoxicity activity. Here, we identified the differential expression of TLR4 and CD14 receptors in AML cell lines and examined their relationship to FA sensitivity. We found that the stimulation of TLR4 with lipopolysaccharide (LPS) in a TLR4-expressing cell line, THP-1, increased cell viability under FA treatment condition and showed that TLR4 stimulation overcame FA sensitivity through the activation of NF-κB, which subsequently upregulated several anti-apoptotic genes. The inhibition of TLR4/NF-κB signaling could partially or completely reverse LPS-induced cell survival under FA treatment conditions. Interestingly, we found that the expression of thioredoxin-interacting protein (TXNIP), a well-known tumor suppressor, was induced by FA treatment; however, it was suppressed by LPS treatment. Furthermore, the expression level of TXNIP was critical for FA-induced cytotoxicity or LPS-induced FA resistance of THP-1?cells. Our data suggest that TXNIP plays an important role in FA-induced cytotoxicity and TLR4/NF-κB-mediated FA resistance of AML cells. Therefore, TXNIP may be a potential therapeutic target for AML treatment.-
dc.publisherElsevier-
dc.titleTLR4/NF-κB axis induces fludarabine resistance by suppressing TXNIP expression in acute myeloid leukemia cells-
dc.title.alternativeTLR4/NF-κB axis induces fludarabine resistance by suppressing TXNIP expression in acute myeloid leukemia cells-
dc.typeArticle-
dc.citation.titleBiochemical and Biophysical Research Communications-
dc.citation.number0-
dc.citation.endPage40-
dc.citation.startPage33-
dc.citation.volume506-
dc.contributor.affiliatedAuthorTae-Don Kim-
dc.contributor.affiliatedAuthorWon Sam Kim-
dc.contributor.affiliatedAuthorDong Oh Kim-
dc.contributor.affiliatedAuthorJae-Eun Byun-
dc.contributor.affiliatedAuthorMi Jeong Kim-
dc.contributor.affiliatedAuthorYoung-Jun Park-
dc.contributor.affiliatedAuthorSuk Ran Yoon-
dc.contributor.affiliatedAuthorJi Yoon Noh-
dc.contributor.affiliatedAuthorJung Woon Lee-
dc.contributor.affiliatedAuthorIn Pyo Choi-
dc.contributor.affiliatedAuthorHaiyoung Jung-
dc.contributor.alternativeNameHuy-
dc.contributor.alternativeName김태돈-
dc.contributor.alternativeName김원삼-
dc.contributor.alternativeName김동오-
dc.contributor.alternativeName변재은-
dc.contributor.alternativeName김미정-
dc.contributor.alternativeName박영준-
dc.contributor.alternativeName윤석란-
dc.contributor.alternativeName노지윤-
dc.contributor.alternativeName이정운-
dc.contributor.alternativeName이규형-
dc.contributor.alternativeName최인표-
dc.contributor.alternativeName정해용-
dc.identifier.bibliographicCitationBiochemical and Biophysical Research Communications, vol. 506, pp. 33-40-
dc.identifier.doi10.1016/j.bbrc.2018.10.047-
dc.subject.keywordAML-
dc.subject.keywordFludarabine-
dc.subject.keywordNF-κB-
dc.subject.keywordTLR4-
dc.subject.keywordTXNIP-
dc.subject.localAML-
dc.subject.localFludarabine-
dc.subject.localNFkappaB-
dc.subject.localNFκB-
dc.subject.localNf-κB-
dc.subject.localNf-κb-
dc.subject.localNuclear factor (NF)-κB-
dc.subject.localNuclear factor kappa B-
dc.subject.localNuclear factor kappaB-
dc.subject.localNuclear factor κB-
dc.subject.localNuclear factor κB (NF-κB)-
dc.subject.localNuclear factor-kappa B-
dc.subject.localNuclear factor-kappa B (NF-κB)-
dc.subject.localNuclear factor-kappaB-
dc.subject.localNuclear factor-κB-
dc.subject.localNuclear factor-κb-
dc.subject.localNF-kB-
dc.subject.localNF-kappa B-
dc.subject.localNF-kappaB-
dc.subject.localNF-ΚB-
dc.subject.localNF-κ B-
dc.subject.localNF-κB-
dc.subject.localNF-κB (nuclear factor kappa-B)-
dc.subject.localnuclear factor kappa B-
dc.subject.localnuclear factor κB-
dc.subject.localnuclear factor-kappaB-
dc.subject.localnuclear factor-kappaB (NF-κB)-
dc.subject.localnuclear factor-κB-
dc.subject.localnuclear factorκB-
dc.subject.localTLR4-
dc.subject.localToll-like receptor 4-
dc.subject.localToll-like receptor 4 (TLR4)-
dc.subject.localToll-like-receptor4-
dc.subject.localTXNIP-
dc.description.journalClassY-
Appears in Collections:
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
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