title: Estrogen upregulates inflammatory signals through NF-κB, IFN-γ, and nitric oxide via Akt/mTOR pathway in the lymph node lymphocytes of middle-aged female rats.
abstract: The alterations in the secretion of sex steroids, especially estrogen, in females throughout reproductive life and its decline with age alters the functions of the neuroendocrine-immune network and renders them susceptible to age-related diseases and cancers. This study investigates the mechanisms of estrogen-induced alterations in cell-mediated immune and inflammatory responses in the lymphocytes from lymph nodes (axillary and inguinal) of ovariectomized (OVX) middle-aged female rats. Ovariectomized middle-aged (MA) Sprague-Dawley female rats (n=8) were implanted with 17β-estradiol (E2) 30-day release pellets (0.6 and 300μg). At the end of the treatment period, lymph nodes (axillary and inguinal) were isolated and examined for serum 17β-estradiol, lymphoproliferation, cytokine production, expression of p-Akt, p-mTOR, p-IκB-α and p-NF-κB (p50 and p65), extent of lipid peroxidation, nitric oxide (NO) production, cytochrome c oxidase activity and reactive oxygen species (ROS) production. There was an OVX-related decline in serum 17β-estradiol level, Con A-induced lymphoproliferation, p-Akt and p-mTOR expression, and cytochrome c oxidase (COX) activity. E2 supplementation increased serum 17β-estradiol level, lymphoproliferation, expression of p-Akt, p-mTOR, p-IκB-α and p-NF-κB (p50 and p65), lipid peroxidation, IFN-γ, TNF-α, ROS and NO production, while it decreased IL-6 production. E2 mediates inflammatory responses by increasing the levels of NO and TNF-α by up regulating IFN-γ and simultaneously promotes aging through the generation of free radicals as reflected by increased lipid peroxidation and ROS production in lymph nodes. These findings may have wide implications to immunity and inflammatory disorders including autoimmune diseases predominantly prevalent in females.
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
authors.forename: Uday P
authors.initials: UP
authors.lastname: Pratap
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
authors.forename: Himanshu R
authors.initials: HR
authors.lastname: Sharma
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Mohanty
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
authors.forename: Prathamesh
authors.initials: P
authors.lastname: Kale
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Gopinath
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
authors.forename: Lalgi
authors.initials: L
authors.lastname: Hima
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Priyanka
authors.affiliation: Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603 203, Tamil Nadu, India. Electronic address: thyagarajan.s@ktr.srmuniv.ac.in.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: ThyagaRajan
mesh_terms: D000375:Aging; D000818:Animals; D003124:Colorimetry; D004343:Drug Implants; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D015227:Lipid Peroxidation; D008163:Luminescent Measurements; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004343:Drug Implants; D004967:Estrogens; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007371:Interferon-gamma; D003576:Electron Transport Complex IV; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Aging; Cytokine; Free radicals; Inflammation; Lipid peroxidation