Effects of mycophenolic acid (MPA) treatment on expression of Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIgR) mRNA in adult sheep tissues.
OBJECTIVE
To quantify the expression of Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIgR) mRNA under a long-term influence of mycotoxin mycophenolic acid (MPA), which is used in human transplantation medicine due to its immunosuppressive properties and is a common contaminant in silage.


METHODS
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 receptor mRNA was determined in eight different adult ovine tissues (liver, kidney, jejunum, ileum, spleen, thymus, mesenteric and pharyngeal lymph nodes). For a reliable and sensitive mRNA 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 pIgR mRNA. 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 by MPA 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 pIgR mRNA was the following: liver > kidney > jejunum > ileum > pharyngeal lymph node > spleen > thymus > mesenterial lymph node.


CONCLUSIONS
The MPA exhibited immunomodulatory effects in the liver and ileum of treated sheep. Its possible immunosuppressive effects may 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.
Dzidic
Anamarija
A
Institute of Physiology, FML-Weihenstephan, Center of Life and Food Science, Technical University of Munich, Weihenstephaner, Freising-Weihenstephan, Germany.
Mohr
Anna
A
Meyer
Karsten
K
Bauer
Johann
J
Meyer
Heinrich H D
HH
Pfaffl
Michael W
MW
D000818:Animals; D008297:Male; D009173:Mycophenolic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D011961:Receptors, Fc / Q000187:drug effects* / Q000378:metabolism; D019056:Receptors, Polymeric Immunoglobulin / Q000187:drug effects* / Q000378:metabolism; D012756:Sheep
D012333:RNA, Messenger; D011961:Receptors, Fc; D019056:Receptors, Polymeric Immunoglobulin; D009173:Mycophenolic Acid