IngentaConnect Phenothiazine-induced increase in thyroid autoantigens and costim...

Authors: Takorabet¹; Ropars¹; Stasiuk¹; Raby²; Charreire¹

Source: Clinical & Experimental Immunology, Volume 111, Number 2, February 1998 , pp. 415-421(7)

Abstract:

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.

Keywords: autoimmunity; experimental autoimmune thyroiditis; thyroid antigens; alimemazine

Document Type: Original article

DOI: 10.1046/j.1365-2249.1998.00507.x

Affiliations: 1: INSERM U283, Université René Descartes, Hôpital Cochin, Paris, 2: Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Limoges, France

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Phenothiazine-induced increase in thyroid autoantigens and costimulatory molecules on thyroid cells: a pathophysiological mechanism for drug-induced autoimmunity?