PMID- 21621594 OWN - NLM STAT- MEDLINE DCOM- 20110906 LR - 20141120 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 205 IP - 1 DP - 2011 Aug 10 TI - Novel gene markers of immunosuppressive chemicals in mouse lymph node assay. PG - 79-85 LID - 10.1016/j.toxlet.2011.05.1017 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Oshida, Keiyu AU - Oshida K AD - Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1, Tebiro, Kamakura, Kanagawa 248-8555, Japan. FAU - Maeda, Akihisa AU - Maeda A FAU - Kitsukawa, Mika AU - Kitsukawa M FAU - Suga, Sachiko AU - Suga S FAU - Iwano, Shunsuke AU - Iwano S FAU - Miyoshi, Tomoya AU - Miyoshi T FAU - Miyamoto, Yohei AU - Miyamoto Y LA - eng PT - Journal Article DEP - 20110520 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Alkylating Agents) RN - 0 (Antimetabolites) RN - 0 (Calcineurin Inhibitors) RN - 0 (Genetic Markers) RN - 0 (Immunosuppressive Agents) RN - 0 (Steroids) RN - 368GB5141J (Sodium Dodecyl Sulfate) RN - 63231-63-0 (RNA) SB - IM MH - Alkylating Agents/pharmacology MH - Animals MH - Antimetabolites/pharmacology MH - Body Weight/drug effects MH - Calcineurin Inhibitors MH - Female MH - Gene Expression/drug effects MH - Genetic Markers MH - Immunosuppressive Agents/*pharmacology MH - *Local Lymph Node Assay MH - Lymph Nodes/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred CBA MH - Oligonucleotide Array Sequence Analysis MH - Organ Size/drug effects MH - RNA/biosynthesis/isolation & purification MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sodium Dodecyl Sulfate/toxicity MH - Steroids/pharmacology EDAT- 2011/05/31 06:00 MHDA- 2011/09/07 06:00 CRDT- 2011/05/31 06:00 PHST- 2011/02/02 00:00 [received] PHST- 2011/05/11 00:00 [revised] PHST- 2011/05/12 00:00 [accepted] PHST- 2011/05/31 06:00 [entrez] PHST- 2011/05/31 06:00 [pubmed] PHST- 2011/09/07 06:00 [medline] AID - S0378-4274(11)01217-3 [pii] AID - 10.1016/j.toxlet.2011.05.1017 [doi] PST - ppublish SO - Toxicol Lett. 2011 Aug 10;205(1):79-85. doi: 10.1016/j.toxlet.2011.05.1017. Epub 2011 May 20.