IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella enteritidis and the impact of IL-10 in bone marrow-derived macrophages.
The members of the IL-12 family of heterodimeric cytokines play a pivotal role in initiation and regulation of cell-mediated immunity. Best known is IL-12p70, which promotes an immune response towards T(h)1 bias. Other members of this family (IL-23, IL-27) are less well characterized in terms of induction and function. Using either heat-killed or viable Salmonella Enteritidis or LPS as a stimulus, the kinetics of mRNA production of each member of the IL-12 family (p19, p28, p35, p40, Ebstein-Barr-Virus-induced gene 3 (EBI-3)) were determined in BMDMPhi originating from wild-type, Toll-like receptor (TLR)2- and/or TLR4-deficient mice. It was found that following either type of stimulation, a characteristic mRNA expression pattern was observed for each cytokine subunit. Whereas p19 was induced early and transiently, p40 and p35 were up-regulated later and then continuously, but the secretion of IL-23 and IL-12p70 was significantly reduced by IL-10. The up-regulation of p28 mRNA occurred also delayed and declined afterwards, whereas the initial high-level expression of EBI-3 remained almost unchanged in BMDMPhi. Furthermore, a splice variant of the EBI-3 mRNA was discovered. In this context, the cytokine mRNA up-regulation by whole Salmonella Enteritidis is mediated chiefly by TLR4, but depends on additional pattern recognition receptors other than TLR2 expressed by macrophages.
Schuetze
Nicole
N
Institute of Immunology, College of Veterinary Medicine and Biotechnological-Biomedical Center (BBZ), University of Leipzig, An den Tierkliniken 11, 04103 Leipzig, Germany.
Schoeneberger
Sabine
S
Mueller
Uwe
U
Freudenberg
Marina A
MA
Alber
Gottfried
G
Straubinger
Reinhard K
RK
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis*; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens; D009569:Nitric Oxide / Q000096:biosynthesis; D021122:Protein Subunits / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D018121:Receptors, Cytokine / Q000096:biosynthesis; D012477:Salmonella enteritidis / Q000276:immunology*
C499601:Ebi3 protein, mouse; C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D021122:Protein Subunits; D018121:Receptors, Cytokine; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D012313:RNA