Macrophage migration inhibitory factor suppresses transforming growth factor-beta2 secretion in cultured rat testicular peritubular cells.
Cytokines have direct effects on testicular cell functions and a number of cytokines are produced constitutively within the testis, even in the absence of immune-activation events. There is clear evidence that cytokines play a dual role as important regulatory factors in the normal function of the testis, as well as in testicular inflammation. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) is expressed locally in the testis and has direct effects on peritubular cells, which, in turn, produce anti-inflammatory mediators, including transforming growth factor (TGF)-(2)2. In the present study, we investigated the function of MIF by examining its effect on the secretion of TGF-(2)2 in peritubular cells. Expression of TGF-(2)2 mRNA was shown by reverse transcription-polymerase chain reaction in peritubular cells isolated from 19-day-old rat testis. The addition of recombinant MIF to cultured peritubular cells resulted in a dose-dependent decrease in TGF-(2)2 secretion up to 52% of control levels after 48 h, which was significant for all doses investigated (10-100 ng mL(-1) MIF). Inhibition of TGF-(2)2 secretion was sustained for 72 h for the highest dose of MIF used (100 ng mL(-1)). No effect of MIF was observed on TGF-(2)2 mRNA expression levels, as shown by real-time polymerase chain reaction. These results suggest that the pro-inflammatory cytokine MIF can shift the cytokine balance from the immunosuppressive state towards an inflammatory reaction, potentially through the inhibition of TGF-(2)2 secretion by peritubular cells.
Müller
Ruth
R
Department of Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
Klug
Jörg
J
Rodewald
Miriam
M
Meinhardt
Andreas
A
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2
D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2