title: Differential roles of Annexin A1 (ANXA1/lipocortin-1/lipomodulin) and thioredoxin binding protein-2 (TBP-2/VDUP1/TXNIP) in glucocorticoid signaling of HTLV-I-transformed T cells.
abstract: Glucocorticoid (GC) is widely used for therapeutic purposes in immunological and hematological disorders. Annexin A1 (ANXA1/lipocortin-1/lipomodulin), a GC-inducible molecule, was regarded as a vital anti-inflammatory mediator of GC. Thioredoxin binding protein-2 (TBP-2/VDUP1/TXNIP), a regulator of redox reactions, cell growth and lipid metabolism, was also reportedly induced by GC. HTLV-I infected T cells undergo the transition from the IL-2 dependent to IL-2 independent growth during the long-term culture in vitro. We found that these T cells responded to GC with growth arrest and apoptosis in the IL-2 dependent growth stage, whereas they failed to respond to GC after their growth had shifted into the IL-2 independent stage. Here we employed these T cell lines and studied the roles of ANXA1 and TBP-2 in mediating GC-induced apoptosis. In GC-sensitive T cells, ANXA1 expression was negligible and unaffected by GC treatment, whereas TBP-2 was expressed and induced by GC treatment. In GC-resistant T cells, however, ANXA1 was highly expressed regardless of GC treatment and promoted cellular proliferation. In contrast, TBP-2 expression was lost and could not mediate the GC-induced apoptosis. In conclusion, these results suggest that TBP-2, but not ANXA1, is directly involved in the switching of GC sensitivity and GC resistance in HTLV-I infected T cell lines, whereas ANXA1 may be a biomarker indicative of the advanced stage of the transformation.
authors.affiliation: Laboratory of Infection and Prevention, Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshihara
authors.forename: Aoi
authors.initials: A
authors.lastname: Son
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masutani
authors.forename: Katsuji
authors.initials: K
authors.lastname: Sugie
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Maeda
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell; D008213:Lymphocyte Activation; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology / Q000821:virology*
chemical_list: D017305:Annexin A1; D002352:Carrier Proteins; D005938:Glucocorticoids; D007376:Interleukin-2; C486715:TXNIP protein, human