title: Higher TNFα responses in young males compared to females are associated with attenuation of monocyte adenylyl cyclase expression.
abstract: Tumor necrosis factor α (TNFα) expression is strongly attenuated by the intracellular signaling mediator cyclic adenosine monophosphate (cAMP), which is synthesized by adenylyl cyclase (AC) enzymes. We have compared AC regulation and TNFα production in male and female monocytes, and characterized the role of monocyte AC isoforms in TNFα regulation. Males and females, age groups 20-30 years and 50-70 years donated blood for this study. In lipopolysaccharide-stimulated blood from young male donors, we observed significantly higher TNFα responses (6h, p=0.03) compared to females of the same age, a difference not observed in the older donors. Rapid down-regulation of the monocyte AC isoforms AC4, AC7 and AC9 were observed in young males. AC-directed siRNA experiments in the human monocyte cell line THP-1 demonstrated that AC7 and AC9 knock-down significantly induced TNFα release (p=0.01 for both isoforms). These data indicate that the stronger TNFα-responses in young males may be partly associated with male-specific down-regulation of adenylyl cyclases.
authors.affiliation: Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Petter K
authors.initials: PK
authors.lastname: Risøe
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Arkady
authors.initials: A
authors.lastname: Rutkovskiy
authors.affiliation: Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ågren
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Ingrid B M
authors.initials: IB
authors.lastname: Kolseth
authors.affiliation: Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Signe Flood
authors.initials: SF
authors.lastname: Kjeldsen
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Guro
authors.initials: G
authors.lastname: Valen
authors.affiliation: Department of Emergency Medicine and Intensive Care, Institute of Clinical Medicine, Oslo University Hospital Ulleval, University of Oslo, Norway.
authors.forename: Jarle
authors.initials: J
authors.lastname: Vaage
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway; Section of Immunology, Norwegian Veterinary Institute, Oslo, Norway. Electronic address: maria.dahle@vetinst.no.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Dahle
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000368:Aged; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C413923:adenylate cyclase 9; C406262:adenylyl cyclase 4; C473265:adenylyl cyclase 7
keywords: Adenylyl cyclase; Gender; Lipopolysaccharide; Monocytes; Tumor necrosis factor alpha