title: Smokeless tobacco extract decreases IL-12 production from LPS-stimulated but increases IL-12 from IFN-gamma-stimulated macrophages.
abstract: Modulation of IFN-gamma production from T cells by smokeless tobacco extract (STE) could be a factor in periodontal disease. The major inducer of IFN-gamma from T cells is bioactive IL-12 (p70), a heterodimeric protein composed of p35 and p40 subunits, while homodimeric IL-12 p40 antagonizes bioactive IL-12. Both p70 and p40 are produced by macrophages in response to lipopolysaccharide (LPS), IFN-gamma and/or CD40 ligation. To determine the impact of STE on IL-12 p40, p70 and IFN-gamma, splenic T cells were stimulated with anti-CD3 while splenic macrophages were stimulated with LPS in the presence or absence of STE. Production of IL-12 p40 and p70 from LPS-stimulated splenic macrophages and IL-12 p40, p70 and IFN-gamma from LPS/anti-CD3-stimulated T cells and macrophages was decreased by STE. To determine the impact of STE on macrophage IL-12 production alone, splenic or peritoneal macrophages were enriched and then stimulated. STE significantly diminished production of IL-12 p40 and p70 from LPS-stimulated peritoneal macrophages, LPS/IFN-gamma-stimulated peritoneal and splenic macrophages, but increased production of IL-12 p40 and p70 from IFN-gamma/CD40-stimulated splenic macrophages or IFN-gamma-stimulated peritoneal macrophages. None of the effects of STE on IL-12 was due to nicotine, rutin or chlorogenic acid. In contrast to STE, nicotine at 100 microg/ml significantly elevated production of IL-12 p40 and p70 from splenic macrophages stimulate by IFN-gamma/LPS. The results indicate that STE has a significant overall effect upon IL-12 production. It suppresses p40 and p70 production during responses to LPS or LPS/IFN-gamma but augments p40 and p70 production during responses to IFN-gamma without LPS. This affect could have a major impact on diseases associated with excessive production of IL-12.
authors.affiliation: Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln 68583-0740, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Petro
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Anderson
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Gowler
authors.forename: Xiao Juan
authors.initials: XJ
authors.lastname: Liu
authors.forename: Steven D
authors.initials: SD
authors.lastname: Schwartzbach
mesh_terms: D000818:Animals; D002726:Chlorogenic Acid / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009538:Nicotine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D012431:Rutin / Q000494:pharmacology; D014030:Tobacco, Smokeless / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D010936:Plant Extracts; D018664:Interleukin-12; D002726:Chlorogenic Acid; D012431:Rutin; D009538:Nicotine; D007371:Interferon-gamma