Immune-Suppression in Sheep via MPA
Effects of Mycophenolic Acid (MPA) Treatment on Expression of Fc Receptor (FcRn) and
Polymeric Immunoglobulin Receptor (pIgR) mRNA in Adult Sheep Tissues
Anamarija Didiæ, Anna Mohr1, Karsten Meyer1, Johann Bauer1, Heinrich H.D. Meyer, Michael W. Pfaffl
Croatian Medical Journal 2004 45(2) 130-135
Institute of Physiology and 1 Institute of Animal Hygiene, FML-Weihenstephan, Center of Life and Food Science,
Technical University of Munich, Freising-Weihenstephan, Germany
Aim. To quantify the expression of Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIgR) mRNA under a long-term influence of mycotoxinmycophenolic acid (MPA),which is used in human transplantationmedicine due to its immunosuppressive properties and is a common contaminant in silage.
Method. We applied 300 mg MPA/day in nine sheep for nine weeks and compared them with untreated animals (n=9). The expression level of Ig receptormRNAwas determined in eight different adult ovine tissues (liver, kidney, jejunum, ileum, spleen, thymus, mesenteric and pharyngeal lymph nodes). For a reliable and sensitivemRNA quantification of Ig receptor subtypes, a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used with a relative- and tissue-specific efficiency corrected quantification model (REST).
Results. Each tissue exhibited an individual expression pattern of FcRn and pIgRmRNA. Both types of Ig receptors were highly expressed in the liver, kidney, and gastrointestinal tract.Medium-to-low expressions were found in the spleen, thymus, mesenteric and pharyngeal lymph nodes. FcRn mRNA was significantly down-regulated byMPA in the liver (p=0.02). After MPA treatment, a significant up-regulation of pIgR mRNA expression was observed in the ileum and liver (p=0.04 for both). Expression level of FcRn mRNA in the tissues in decreasing order was as follows: liver>kidney>jejunum>ileum>spleen>thymus>mesenterial lymph node>pharyngeal lymph node;whereas expression level for pIgRmRNAwas the following: liver>kidney>jejunum>ileum>pharyngeal lymph node>spleen
> thymus > mesenterial lymph node.
Conclusion. The MPA exhibited immunomodulatory effects in the liver and ileum of treated sheep. Its possible immunosuppressive effectsmay be explained by lowering the level of FcRn expression in the liver,which resulted in a lower IgG serum-to-bile transport. However, MPA showed stimulatory effects on pIgR expression in the liver and ileum, suggesting good IgA and IgM transport in these tissues.