Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0010868
Title: Mutually positive regulatory feedback loop between interferons and estrogen receptor-? in mice: Implications for sex bias in autoimmunity
Authors: Panchanathan R.
Shen H. 
Zhang X.
Ho S.
Choubey D.
Keywords: alpha interferon
estrogen
estrogen receptor alpha
gamma interferon
messenger RNA
STAT1 protein
animal cell
animal cell culture
article
autoimmunity
cell stimulation
controlled study
female
gender bias
gene expression regulation
gene function
gene targeting
genetic association
immunoregulation
interferon induction
intracellular signaling
male
mouse
nonhuman
positive feedback
promoter region
protein expression
receptor upregulation
spleen cell
steady state
systemic lupus erythematosus
transcription initiation
transcription regulation
wild type
Animals
Autoimmunity
Cell Line, Tumor
Estradiol
Estrogen Receptor alpha
Feedback, Physiological
Female
Gene Expression Regulation, Neoplastic
Interferons
Male
Mice
Mice, Inbred C57BL
RNA, Messenger
Sex Characteristics
Signal Transduction
STAT1 Transcription Factor
Transcription, Genetic
Murinae
Mus
Issue Date: 2010
Citation: Panchanathan R., Shen H., Zhang X., Ho S., Choubey D. (2010). Mutually positive regulatory feedback loop between interferons and estrogen receptor-? in mice: Implications for sex bias in autoimmunity. PLoS ONE 5 (5) : e10868. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0010868
Abstract: Background:Systemic lupus erythematosus (SLE), an autoimmune disease, predominantly affects women of childbearing age. Moreover, increased serum levels of interferon-a (IFN-?) are associated with the disease. Although, the female sex hormone estrogen (E2) is implicated in sex bias in SLE through up-regulation of IFN-? expression, the molecular mechanisms remain unknown. Here we report that activation of IFN (? or ?)-signaling in immune cells up-regulates expression of estrogen receptor-a (ERa; encoded by the Esr1 gene) and stimulates expression of target genes. Methodology/Principal Findings:We found that treatment of mouse splenic cells and mouse cell lines with IFN (? or ?) increased steady-state levels of ER? mRNA and protein. The increase in the ER? mRNA levels was primarily due to the transcriptional mechanisms and it was dependent upon the activation of signal transducer and activator of transcription-1 (STAT1) factor by IFN. Moreover, the IFN-treatment of cells also stimulated transcription of a reporter gene, expression of which was driven by the promoter region of the murine Esr1 gene. Notably, splenic cells from pre-autoimmune lupus-prone (NZB × NZW)F1 female mice had relatively higher steady-state levels of mRNAs encoded by the IFN and ER?-responsive genes as compared to the age-matched males. Conclusions/Significance:Our observations identify a novel mutually positive regulatory feedback loop between IFNs and ERa in immune cells in mice and support the idea that activation of this regulatory loop contributes to sex bias in SLE. © 2010 Panchanathan et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161809
ISSN: 19326203
DOI: 10.1371/journal.pone.0010868
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