Phenothiazine-induced increase in thyroid autoantigens and costimulatory molecules on thyroid cells: a pathophysiological mechanism for drug-induced autoimmunity?
We have previously demonstrated (J Immunol 1995; 154:3593) that MHC class II antigens can be induced on thyroid epithelial cells (TEC) by alimemazine, a member of the phenothiazine group. Although this expression of MHC class II antigens on TEC confers the theoretical ability to behave as antigen-presenting cells (APC), the simultaneous expression of self antigens and co-receptor(s) must also occur for efficient presentation of self antigens. Therefore, we investigated whether alimemazine applied at pharmacologic doses would modify the expression of thyroid antigens, and simultaneously, the expression of intercellular adhesion molecule-1 (ICAM-1), B7, and LFA-1 co-receptors in human TEC in culture. Using polymerase chain reaction (PCR) amplification and Northern blot analysis, we showed that alimemazine induces increases in thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) cDNA, within the first 2 h following its addition. This phenomenon is followed 48 h later by an increase of Tg and TSH-R protein expression on the surface of TEC. Furthermore, increases in the expression of ICAM-1 and B7 co-receptors were concomitantly observed. These results suggest that alimemazine, a drug currently used in paediatrics, could play a role in the induction and perpetuation of thyroid autoimmune disorders by transforming TEC into functional APC.
Takorabet
L
L
INSERM U283, Université René Descartes, Hôpital Cochin, Paris, France.
Ropars
A
A
Stasiuk
L
L
Raby
C
C
Charreire
J
J
D000941:Antigens / Q000096:biosynthesis; D000982:Antipruritics / Q000494:pharmacology*; D001324:Autoantigens / Q000096:biosynthesis*; D015551:Autoimmunity / Q000187:drug effects*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D015153:Blotting, Western; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D006825:Hybridomas; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D011989:Receptors, Thyrotropin / Q000096:biosynthesis / Q000235:genetics; D013954:Thyroglobulin / Q000096:biosynthesis / Q000235:genetics; D013961:Thyroid Gland / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000378:metabolism; D014291:Trimeprazine / Q000494:pharmacology*
D000941:Antigens; D000982:Antipruritics; D001324:Autoantigens; D018122:B7-1 Antigen; D018076:DNA, Complementary; D016169:Lymphocyte Function-Associated Antigen-1; D011989:Receptors, Thyrotropin; D018799:Intercellular Adhesion Molecule-1; D014291:Trimeprazine; D013954:Thyroglobulin