PMID- 17612902 OWN - NLM STAT- MEDLINE DCOM- 20071023 LR - 20131121 IS - 0891-6934 (Print) IS - 0891-6934 (Linking) VI - 40 IP - 5 DP - 2007 Jul TI - Lack of effect of methimazole on dendritic cell (DC) function and DC-induced Graves' hyperthyroidism in mice. PG - 397-402 AB - In addition to the biochemical inhibition of thyroid hormone synthesis, antithyroid drugs including methimazole (MMI) may have immunosuppressive effect through inhibition of major histocompatibility complex (MHC) class I and II expressions on non-professional (thyrocytes) and professional (macrophages and B cells) antigen presenting cells (APCs). Dendritic cells (DCs) are another professional APCs and very likely play the most important role in the primary immune response. Therefore, we focused in this study on evaluating the effect of MMI on DC function in mice. Bone marrow cells cultured with granulocyte macrophage colony stimulating factor and interleukin (IL)-4 expressed high levels of CD11c and moderate levels of MHC class II, both of which are widely used markers for DCs. In vitro incubation of this DC-containing cell population with 10(- 6)-10(- 4) M MMI for 2 days did not change basal- and maturation signal (adenoviral infection and lipopolysaccharide)-induced levels of the cell surface marker expressions such as MHC class I and II, CD86, CD40 and DEC205, and of proinflammatory cytokine IL-6 release. Further we found that treatment of the DC-containing cell population with MMI did not influence the incidence of Graves' hyperthyroidism and anti-thyrotropin receptor (TSHR) antibody titers in a mouse Graves' model we have recently established with DCs infected with adenovirus expressing the TSHR A subunit. Although we cannot completely exclude immunosuppressive effect of MMI on other immune cells, our data indicate that DCs do not appear to be the primary target for the immunosuppressive effect of MMI. FAU - Mizutori, Yumiko AU - Mizutori Y AD - Department of Medical Gene Technology, Graduate School of Biomedical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Sakamoto, Nagasaki, Japan. nagayama@nagasaki-u.ac.jp FAU - Saitoh, Ohki AU - Saitoh O FAU - Eguchi, Katsumi AU - Eguchi K FAU - Nagayama, Yuji AU - Nagayama Y LA - eng PT - Journal Article PL - England TA - Autoimmunity JT - Autoimmunity JID - 8900070 RN - 0 (Cytokines) RN - 0 (Histocompatibility Antigens) RN - 0 (Immunosuppressive Agents) RN - 554Z48XN5E (Methimazole) SB - IM MH - Animals MH - Antigen-Presenting Cells/drug effects/immunology/metabolism MH - Cells, Cultured MH - Cytokines/immunology/metabolism MH - Dendritic Cells/drug effects/*immunology/metabolism MH - Female MH - Graves Disease/drug therapy/*immunology MH - Histocompatibility Antigens/immunology/metabolism MH - Immunosuppressive Agents/pharmacology MH - Methimazole/*pharmacology/therapeutic use MH - Mice MH - Mice, Inbred BALB C MH - Thyroid Gland MH - Transfection EDAT- 2007/07/07 09:00 MHDA- 2007/10/24 09:00 CRDT- 2007/07/07 09:00 PHST- 2007/07/07 09:00 [pubmed] PHST- 2007/10/24 09:00 [medline] PHST- 2007/07/07 09:00 [entrez] AID - 779824813 [pii] AID - 10.1080/08916930701463485 [doi] PST - ppublish SO - Autoimmunity. 2007 Jul;40(5):397-402. doi: 10.1080/08916930701463485.