Cyclosporine-A treatment inhibits the expression of metabotropic glutamate receptors in rat thymus.
We have evaluated the expression of metabotropic glutamate receptors (mGluR subtypes 2/3, 4 and 5) in rat thymus under normal and experimental conditions after 2 and 21 days of cyclosporine-A treatment. In normal rats, immunohistochemical analysis showed that expression of mGluRs was high in dendritic cells and lymphocytes of the medulla whereas it was weak in lymphocytes of the cortex. However, there were some differences in the expression of mGluRs subtypes. mGluR5 showed strong expression in lymphocytes of medulla and dendritic cells. mGluR2/3 and mGluR4 were moderately expressed in lymphocytes and dendritic cells of the medulla and weakly in cortical lymphocytes. Immunoblotting showed moderate levels of mGluR2/3 and mGluR4 and strong levels of mGluRS. After 2 days of cyclosporine-A treatment, we observed by immunohistochemistry and immunoblotting a distinct decrease in all mGluRs and their expression had almost completely disappeared after 21 days of treatment. The results clearly indicate that: 1) mGluR2/3, 4 and 5 are widely expressed in thymic cells; 2) the mGluR5 subtype is expressed most strongly in medullary cells; and 3) cyclosporine-A rapidly inhibits expression of all mGluR subtypes after 2 days of treatment and their complete disappearance after prolonged treatment. These findings may indicate a possible mechanism by which cyclosporine-A produces its immunosupressive effects.
Rezzani
Rita
R
Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.
Corsetti
Giovanni
G
Rodella
Luigi
L
Angoscini
Paola
P
Lonati
Claudio
C
Bianchi
Rossella
R
D000818:Animals; D015153:Blotting, Western; D016572:Cyclosporine / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism
D007166:Immunosuppressive Agents; D018094:Receptors, Metabotropic Glutamate; D016572:Cyclosporine