title: Interleukin 10 abolishes the growth inhibitory effects of all-trans retinoic acid on human myeloma cells.
abstract: Recently, it was disclosed that all-trans retinoic acid (ATRA) inhibits myeloma cell growth by downregulating the interleukin 6 (IL-6)/IL-6 receptor (IL-6R) auto/paracrine loop, and upregulating p21/Cip1 cyclin-dependent kinase inhibitor (CDK-I), thereby inducing apoptosis with a decrease in Bcl-2 protein expression. To elucidate and generalize the effects of ATRA on the proliferation and cellular biology of myeloma cells, 12 human myeloma cell lines established in our laboratory were utilized. Two out of the 12 lines showed enhanced growth on supplementation of ATRA and were characterized by IL-10 production, downregulation of membrane Fas and reduced upregulation of p21/Cip1 CDK-I message. These characteristics may prove important for the clinical use of ATRA and should be considered before starting ATRA therapy for myeloma.
authors.affiliation: Department of Hygiene, Division of Hematology, Kawasaki Medical School, Kurashiki, Japan. takemi@med.kawasaki-m.ac.jp
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yata
authors.forename: Haruko
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Junichi
authors.initials: J
authors.lastname: Kurebayashi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Masako
authors.initials: M
authors.lastname: Uno
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujii
authors.forename: Sakura
authors.initials: S
authors.lastname: Eda
authors.forename: Yumika
authors.initials: Y
authors.lastname: Isozaki
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yawata
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamada
authors.forename: Hideho
authors.initials: H
authors.lastname: Wada
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugihara
authors.forename: Ayako
authors.initials: A
authors.lastname: Ueki
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019014:fas Receptor; D016753:Interleukin-10; D014212:Tretinoin; D016203:CDC2 Protein Kinase