title: Cytokine reporter mouse system for screening novel IL12/23 p40-inducing compounds.
abstract: Cytokines interleukin (IL) 12 and 23 play critical roles in linking innate and adaptive immune responses. They are members of heterodimeric cytokines, sharing a subunit p40. Although IL12/23 p40 is mainly induced in macrophages and dendritic cells (DCs) after stimulation with microbial Toll-like receptor ligands, methods to monitor the cells that produce IL12/23 p40 in vivo are limited. Recently, the mouse model to track p40-expressing cells with fluorescent reporter, yellow fluorescent protein, has been developed. Macrophages and DCs from these mice faithfully reported p40 induction using the fluorescent marker. Here we took advantage of these reporter mice to screen bio-compounds for p40-inducing activity. After screening hundreds of compounds, we found several extracts inducing IL12/23 p40 gene expression. Treatment of DCs with these extracts induced the expression of MHC class II and co-stimulatory molecules, which implies that these might be useful as adjuvants. Next, the in vivo target immune cells of candidate compounds were examined. The reporter system can be useful to identify cells producing IL12 or IL23 in vivo as well as in vitro. Thus, our cytokine reporter system proved to be a valuable reagent for screening for immunostimulatory molecules and identification of target cells in vivo.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Im
authors.forename: Hyojeong
authors.initials: H
authors.lastname: Kim
authors.forename: Daesun
authors.initials: D
authors.lastname: Yun
authors.forename: Sung-Yum
authors.initials: SY
authors.lastname: Seo
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
authors.forename: Seokmann
authors.initials: S
authors.lastname: Hong
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D053762:Interleukin-12 Subunit p40; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010936:Plant Extracts / Q000494:pharmacology; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D053762:Interleukin-12 Subunit p40; D010936:Plant Extracts; D021122:Protein Subunits; D018664:Interleukin-12