title: Expression and regulation of interleukin-23 subunits in human peripheral blood mononuclear cells and hematopoietic cell lines in response to various inducers.
abstract: IL-23 is a novel cytokine composed of an IL-12 p40 and a p19 subunit. We analyzed human peripheral blood mononuclear cells (PBMC) and hematopoietic cell lines for constitutive expression of IL-23 and IL-12 subunits and expression following exposure to various stimuli, and investigated the mechanisms of their induction by LPS and SAC. IL-23 p19 and IL-12 p35 mRNAs were expressed in fresh PBMC, and expression of all IL-23 and IL-12 subunits was up-regulated by LPS and SAC. LPS-induced increase of IL-23 and IL-12 subunits expression was CD14-dependent, while CD14 was not involved in SAC-induced p19 transcription. Both LPS- and SAC-induced subunits expression required p38 MAPK pathway. PHA effected an increase of p19 mRNA in both CD4+ and CD8+ T cells, whereas p35 was minimally regulated by PHA. IFN-gamma primed monocytes for LPS stimulation of p19, p35 and p40 expression. p19 mRNA was detectable in most hematopoietic cell lines tested but p35 distribution was more restricted. A phorbol diester enhanced p19, p35 and p40 expression in EBV-positive cell lines. Our results suggest that both the subunits of IL-23 are tightly regulated; the expression pattern and regulation mode of IL-23 p19 is similar to as well as distinct from that of IL-12 p35.
authors.affiliation: National Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, China.
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Ma
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Geng
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Ke-Fu
authors.initials: KF
authors.lastname: Wu
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000502:physiology
chemical_list: C508840:IL23A protein, human; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D008070:Lipopolysaccharides; D021122:Protein Subunits; D018664:Interleukin-12