title: Novel gene markers of immunosuppressive chemicals in mouse lymph node assay.
abstract: The murine local lymph node assay (LLNA) is an immunologically based test of the sensitizing potential of immunotoxicants, but also evaluates immunosuppressive potential with good sensitivity and specificity. We conducted the LLNA with calcineurin inhibitors (tacrolimus and cyclosporin A), antimetabolites (methotrexate and azathioprine), steroids (dexamethasone and prednisolone), and an alkylator (cyclophosphamide). We performed a comprehensive analysis of results of gene expression in lymph nodes obtained in the LLNA using a highly sensitive DNA chip, 3D-Gene™, and the quantitative reverse transcription-polymerase chain reaction (qPCR). Zfp459 expression increased in all animals treated with immunosuppressive chemicals. Ltf, Cbll1 and Lias expression changed specifically in response to the calcineurin inhibitors, Fmo2 and 9630033F20Rik in response to the antimetabolites, Krt8, Gjb1, Hmha1 and Sfrs7 in response to the steroids, and Gbp1 and Mup5 in response to the alkylator. Therefore, these genes were considered novel markers for immunosuppression and their expression could be used to evaluate the mechanism of action of immunosuppressive chemicals.
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Keiyu
authors.initials: K
authors.lastname: Oshida
authors.forename: Akihisa
authors.initials: A
authors.lastname: Maeda
authors.forename: Mika
authors.initials: M
authors.lastname: Kitsukawa
authors.forename: Sachiko
authors.initials: S
authors.lastname: Suga
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Iwano
authors.forename: Tomoya
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamoto
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D065095:Calcineurin Inhibitors; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005819:Genetic Markers; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D013256:Steroids / Q000494:pharmacology
chemical_list: D000477:Alkylating Agents; D000963:Antimetabolites; D065095:Calcineurin Inhibitors; D005819:Genetic Markers; D007166:Immunosuppressive Agents; D013256:Steroids; D012967:Sodium Dodecyl Sulfate; D012313:RNA