Female and male sex hormones differentially regulate expression of Ifi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval

Ravichandran Panchanathan, Hui Shen, Melanie Gubbels Bupp, Karen A Gould, Divaker Choubey

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Increased expression of IFN-inducible Ifi202 gene in certain strains of female mice is associated with susceptibility to systemic lupus erythematosus (SLE). Although, the development of SLE is known to have a strong sex bias, the molecular mechanisms remain unknown. Here we report that in vivo treatment of orchiectomized (NZB x NZW)F1 male mice with the female sex hormone 17β-estradiol significantly increased steady-state levels of Ifi202 mRNA in splenic cells, whereas treatment with the male hormone dihydrotestosterone decreased the levels. Moreover, increased expression of Ifi202 in B6.Nba2 B cells and reduced expression in T cells were associated with increased levels of estrogen receptor-α (ERα) and androgen receptor, respectively. Furthermore, the steady-state levels of Ifi202 mRNA were higher in splenic cells from C57BL/6, B6.Nba2, NZB, and (NZB x NZW)F1 female mice as compared with males. 17β-estradiol treatment of B cells and WT276 cells increased Ifi202 mRNA levels, whereas treatment with dihydrotestosterone decreased the levels. Interestingly, overexpression of ERα in WT276 cells increased the expression of Ifi202 and stimulated the activity of the 202-luc-reporter through the c-Jun/AP-1 DNA-binding site. Accordingly, ERα preferentially associated with the regulatory region of the Ifi202 gene in female B6.Nba2 B cells than in males. Furthermore, Ifi202 mRNA levels were detectable in splenic cells of wild-type (Esr1+/+), but not null (Esr1-/-), (NZB x NZW)F1 female mice. Collectively, our observations demonstrate that the female and male sex hormones differentially regulate the expression of Ifi202, thus providing support for the role of Ifi202 in sex bias in SLE.

Original languageEnglish (US)
Pages (from-to)7031-7038
Number of pages8
JournalJournal of Immunology
Volume183
Issue number11
DOIs
StatePublished - Dec 1 2009

Fingerprint

Gonadal Steroid Hormones
Interferons
Estrogen Receptors
Systemic Lupus Erythematosus
Genes
Sexism
Messenger RNA
B-Lymphocytes
Dihydrotestosterone
Estradiol
Nucleic Acid Regulatory Sequences
Transcription Factor AP-1
Androgen Receptors
Binding Sites
Hormones
T-Lymphocytes
DNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Female and male sex hormones differentially regulate expression of Ifi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval. / Panchanathan, Ravichandran; Shen, Hui; Bupp, Melanie Gubbels; Gould, Karen A; Choubey, Divaker.

In: Journal of Immunology, Vol. 183, No. 11, 01.12.2009, p. 7031-7038.

Research output: Contribution to journalArticle

Panchanathan, Ravichandran ; Shen, Hui ; Bupp, Melanie Gubbels ; Gould, Karen A ; Choubey, Divaker. / Female and male sex hormones differentially regulate expression of Ifi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval. In: Journal of Immunology. 2009 ; Vol. 183, No. 11. pp. 7031-7038.
@article{d15ca6a497e84a72a0518385a455b600,
title = "Female and male sex hormones differentially regulate expression of Ifi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval",
abstract = "Increased expression of IFN-inducible Ifi202 gene in certain strains of female mice is associated with susceptibility to systemic lupus erythematosus (SLE). Although, the development of SLE is known to have a strong sex bias, the molecular mechanisms remain unknown. Here we report that in vivo treatment of orchiectomized (NZB x NZW)F1 male mice with the female sex hormone 17β-estradiol significantly increased steady-state levels of Ifi202 mRNA in splenic cells, whereas treatment with the male hormone dihydrotestosterone decreased the levels. Moreover, increased expression of Ifi202 in B6.Nba2 B cells and reduced expression in T cells were associated with increased levels of estrogen receptor-α (ERα) and androgen receptor, respectively. Furthermore, the steady-state levels of Ifi202 mRNA were higher in splenic cells from C57BL/6, B6.Nba2, NZB, and (NZB x NZW)F1 female mice as compared with males. 17β-estradiol treatment of B cells and WT276 cells increased Ifi202 mRNA levels, whereas treatment with dihydrotestosterone decreased the levels. Interestingly, overexpression of ERα in WT276 cells increased the expression of Ifi202 and stimulated the activity of the 202-luc-reporter through the c-Jun/AP-1 DNA-binding site. Accordingly, ERα preferentially associated with the regulatory region of the Ifi202 gene in female B6.Nba2 B cells than in males. Furthermore, Ifi202 mRNA levels were detectable in splenic cells of wild-type (Esr1+/+), but not null (Esr1-/-), (NZB x NZW)F1 female mice. Collectively, our observations demonstrate that the female and male sex hormones differentially regulate the expression of Ifi202, thus providing support for the role of Ifi202 in sex bias in SLE.",
author = "Ravichandran Panchanathan and Hui Shen and Bupp, {Melanie Gubbels} and Gould, {Karen A} and Divaker Choubey",
year = "2009",
month = "12",
day = "1",
doi = "10.4049/jimmunol.0802665",
language = "English (US)",
volume = "183",
pages = "7031--7038",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "11",

}

TY - JOUR

T1 - Female and male sex hormones differentially regulate expression of Ifi202, an interferon-inducible lupus susceptibility gene within the Nba2 interval

AU - Panchanathan, Ravichandran

AU - Shen, Hui

AU - Bupp, Melanie Gubbels

AU - Gould, Karen A

AU - Choubey, Divaker

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Increased expression of IFN-inducible Ifi202 gene in certain strains of female mice is associated with susceptibility to systemic lupus erythematosus (SLE). Although, the development of SLE is known to have a strong sex bias, the molecular mechanisms remain unknown. Here we report that in vivo treatment of orchiectomized (NZB x NZW)F1 male mice with the female sex hormone 17β-estradiol significantly increased steady-state levels of Ifi202 mRNA in splenic cells, whereas treatment with the male hormone dihydrotestosterone decreased the levels. Moreover, increased expression of Ifi202 in B6.Nba2 B cells and reduced expression in T cells were associated with increased levels of estrogen receptor-α (ERα) and androgen receptor, respectively. Furthermore, the steady-state levels of Ifi202 mRNA were higher in splenic cells from C57BL/6, B6.Nba2, NZB, and (NZB x NZW)F1 female mice as compared with males. 17β-estradiol treatment of B cells and WT276 cells increased Ifi202 mRNA levels, whereas treatment with dihydrotestosterone decreased the levels. Interestingly, overexpression of ERα in WT276 cells increased the expression of Ifi202 and stimulated the activity of the 202-luc-reporter through the c-Jun/AP-1 DNA-binding site. Accordingly, ERα preferentially associated with the regulatory region of the Ifi202 gene in female B6.Nba2 B cells than in males. Furthermore, Ifi202 mRNA levels were detectable in splenic cells of wild-type (Esr1+/+), but not null (Esr1-/-), (NZB x NZW)F1 female mice. Collectively, our observations demonstrate that the female and male sex hormones differentially regulate the expression of Ifi202, thus providing support for the role of Ifi202 in sex bias in SLE.

AB - Increased expression of IFN-inducible Ifi202 gene in certain strains of female mice is associated with susceptibility to systemic lupus erythematosus (SLE). Although, the development of SLE is known to have a strong sex bias, the molecular mechanisms remain unknown. Here we report that in vivo treatment of orchiectomized (NZB x NZW)F1 male mice with the female sex hormone 17β-estradiol significantly increased steady-state levels of Ifi202 mRNA in splenic cells, whereas treatment with the male hormone dihydrotestosterone decreased the levels. Moreover, increased expression of Ifi202 in B6.Nba2 B cells and reduced expression in T cells were associated with increased levels of estrogen receptor-α (ERα) and androgen receptor, respectively. Furthermore, the steady-state levels of Ifi202 mRNA were higher in splenic cells from C57BL/6, B6.Nba2, NZB, and (NZB x NZW)F1 female mice as compared with males. 17β-estradiol treatment of B cells and WT276 cells increased Ifi202 mRNA levels, whereas treatment with dihydrotestosterone decreased the levels. Interestingly, overexpression of ERα in WT276 cells increased the expression of Ifi202 and stimulated the activity of the 202-luc-reporter through the c-Jun/AP-1 DNA-binding site. Accordingly, ERα preferentially associated with the regulatory region of the Ifi202 gene in female B6.Nba2 B cells than in males. Furthermore, Ifi202 mRNA levels were detectable in splenic cells of wild-type (Esr1+/+), but not null (Esr1-/-), (NZB x NZW)F1 female mice. Collectively, our observations demonstrate that the female and male sex hormones differentially regulate the expression of Ifi202, thus providing support for the role of Ifi202 in sex bias in SLE.

UR - http://www.scopus.com/inward/record.url?scp=73349110966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73349110966&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0802665

DO - 10.4049/jimmunol.0802665

M3 - Article

C2 - 19890043

AN - SCOPUS:73349110966

VL - 183

SP - 7031

EP - 7038

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 11

ER -