T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells.
We investigated the regulatory influence of several cytokines on the expression of preproenkephalin (PPE) mRNA in human peripheral blood mononuclear cells (PBMC). By use of a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), we demonstrate that the T helper 2 cytokines IL-4 and IL-10 are more potent in upregulating PPE mRNA expression in human PBMC than the T helper 1 cytokines IL-2 and gamma-IFN. In addition, TGF-beta is also an effective inducer of PPE mRNA. TGF-beta, IL-4 and IL-10 increase the cytoplasmatic concentration of met-enkephalin in PBMC. Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated. IL-4 and IL-10 do not induce PPE mRNA via the same pathways. We could observe that PKA is involved in IL-4 mediated PPE mRNA induction, whereas IL-10 apparently uses another route.
Kamphuis
S
S
Department of Immunology, University Hospital for Children and Youth, Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands. s.kamphuis@wkz.ruu.nl
Kavelaars
A
A
Brooimans
R
R
Kuis
W
W
Zegers
B J
BJ
Heijnen
C J
CJ
D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D000242:Cyclic AMP / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D009000:Monocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic
D003470:Culture Media; D016207:Cytokines; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D016753:Interleukin-10; D015847:Interleukin-4; D004744:Enkephalin, Methionine; C033660:preproenkephalin; D000242:Cyclic AMP