Estrogen increases, whereas IL-27 and IFN-γ decrease, splenocyte IL-17 production in WT mice

Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060-0342, USA.
European Journal of Immunology (Impact Factor: 4.52). 09/2010; 40(9):2549-56. DOI: 10.1002/eji.201040303
Source: PubMed

ABSTRACT Estrogen-mediated regulation of Th1, Th2 and Treg effector functions are well documented but, surprisingly, there is little information whether estrogen modulates IL-17, a powerful proinflammatory cytokine that plays a pivotal role in several inflammatory and autoimmune diseases. Therefore in the current study, we determined whether estrogen regulates the expression levels of IL-17 in WT C57BL/6 mice. By ELISA, ELISPOT and/or flow cytometric analyses, we found that estrogen upregulated the levels of not only IL-17, but also the IL-17-specific transcription factor retinoic acid-related orphan receptor gamma t (ROR gamma t), in activated splenocytes. IL-17 levels were further enhanced by exposure of activated splenocytes to IL-23, particularly in cells from estrogen-treated mice. Exposure of splenocytes to IL-27 or IFN-gamma at the time of activation markedly inhibited the levels of IL-17 and ROR gamma t. Interestingly, a delay of 24 h in exposure of activated splenocytes to IL-27 or IFN-gamma decreased IL-17 levels (albeit less profoundly) but not ROR gamma t. These findings imply that the suppressive effects of IL-27 and IFN-gamma are more effective prior to the differentiation and commitment of IL-17-secreting cells. Furthermore, inhibition of JAK-2 by AG490 suppressed IL-17 but not ROR gamma t expression, suggesting that other transcription factors are also critical in estrogen-mediated upregulation of IL-17.

Download full-text


Available from: Deena Khan, Jul 29, 2015
  • Source
    • "Estrogen also enhances B cell activation (Paavonen, Andersson et al. 1981), IgG production (Kanda and Tamaki 1999), and upregulates activation-induced deaminase (AID), thereby enhancing somatic hypermutation frequency and class-switch recombination, resulting in greater antibody affinity-maturation (Karpuzoglu and Zouali 2011). In vitro studies examining the effect of E2 on T cell proliferation and cytokine production have often yielded contradictory results when using PBMC (Bouman, Heineman et al. 2005) although some observations do suggest a potential bias towards Th2, Th17 (Polanczyk, Hopke et al. 2006) and Treg polarization in E2 treated T cell cultures (Khan, Dai et al. 2010). "
    Sex Steroids, 01/2012; , ISBN: 978-953-307-857-1
  • [Show abstract] [Hide abstract]
    ABSTRACT: MC-CDMA, which is based on OFDM and CDMA, is a major candidate for systems beyond IMT-2000. A time-domain spreading MC-CDMA system that has consecutive pilot symbols can achieve high quality channel estimation in fast fading environments. Furthermore, it is known that time-domain spreading MC-CDMA is suited to the use of AMC (adaptive modulation and channel coding). MC-CDMA based on OFDM generally has a guard interval (GI), which is a cyclic prefix to avoid the intersymbol interference (ISI) and interchannel interference (ICI) caused by delay paths. The receiving characteristics of MC-CDMA are significantly degraded by ISI and ICI when there are delayed paths that exceed the GI. To accurately estimate the transmission characteristics, we need an accurate delay profile model that well reflects actual delay profiles. The existing model is, however, very complicated, so it cannot be used in computer simulations. We propose an extremely simple equivalent path model for time-domain code spreading MC-CDMA; it consists of just two paths but its transmission characteristics are reasonable if the delay profile has paths that exceed GI. Computer simulation results validate the proposed model. Moreover, we consider a parameter to characterize the model with which we transform an arbitrary path model into the equivalent path model.
    Vehicular Technology Conference, 2004. VTC 2004-Spring. 2004 IEEE 59th; 06/2004
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a multifaceted range of symptoms affecting almost every organ system. The prototypical pathology of SLE involves the production of antinuclear antibodies and the deposition of immune complexes in basement membranes throughout the body where they induce inflammatory responses. The genetic and environmental etiologies of this process are being intensively sought, and recently, T H 17 cells have been implicated in the pathogenesis of SLE. T H 17 cells are CD4+ memory T cells that behave as both helper and effector cell populations functioning through their signature IL-17 cytokines. Their differentiation is distinct to either the T H 1 or T H 2 cell lineage, but strongly influences development of adaptive responses, including autoimmunity. This paper details the biological functions and regulation of T H 17 cells, followed by an update of their expanding role in SLE.
    03/2011; 2011(2090-1984):810649. DOI:10.1155/2011/810649
Show more