Effect of Estrogens on the Interferon-γ Producing Cell Population of Mouse Splenocytes

Nakaya, Masato; Tachibana, Hirofumi; Yamada, Koji

doi:10.1271/bbb.70.47

Cited by 65 publications

(48 citation statements)

References 34 publications

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“…The decreased IRF-1 in splenocytes from estrogentreated mice, which were activated with T-cell stimulants, was surprising considering that we and others have shown that estrogen promotes IFN-g, a cytokine that induces IRF-1 (Fox et al 1991, Karpuzoglu-Sahin et al 2001, Maret et al 2003, Gourdy et al 2005, Nakaya et al 2006. The importance of IFN-g in IRF-1 induction is evidenced by the findings that IRF-1 was markedly decreased in Con-A-activated splenocytes from IFN-g K / K mice.…”

Section: Discussionmentioning

confidence: 94%

17β-Estradiol downregulates interferon regulatory factor-1 in murine splenocytes

Lengi¹,

Phillips²,

Karpuzoglu³

et al. 2006

Journal of Molecular Endocrinology

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Interferon regulatory factor-1 (IRF-1) is an important transcription factor that mediates interferon-g (IFN-g)-induced cellsignaling events. In this study, we examined whether 17b-estradiol alters IRF-1 in splenic lymphocytes, in view of the immunomodulatory effects of this natural female sex hormone including its ability to alter IFN-g levels. We find that IRF-1 expression is markedly downregulated in splenocytes or purified T-cells from estrogen-treated mice at all time points studied when compared with their placebo counterparts. This decrease in IRF-1 in splenocytes from estrogen-treated mice is neither due to upregulation of IRF-1-interfering proteins (nucleophosmin or signal transducer and activator of transcription (STAT)-5) nor due to alternatively spliced IRF-1 mRNA. Given that IFN-g is a potent inducer of IRF-1, direct addition of recombinant IFN-g to splenocytes from either wild-type or IFN-g-knockout mice, or the addition of recombinant IFN-g to purified T-cells, was expected to stimulate IRF-1 expression. However, robust expression of IRF-1 in cells from estrogen-treated mice was not seen, unlike what was observed in cells from placebo-treated mice. Diminished IFN-g induction of IRF-1 in cells from estrogen-treated mice was noticed despite comparable phosphorylated STAT-1 activation. These studies are the first to show that estrogen regulates IFN-g-inducible IRF-1 in lymphoid cells, a finding that may have implications to IFN-g-regulated immune and vascular diseases.

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Section: Discussionmentioning

confidence: 94%

17β-Estradiol downregulates interferon regulatory factor-1 in murine splenocytes

Lengi¹,

Phillips²,

Karpuzoglu³

et al. 2006

Journal of Molecular Endocrinology

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“…Increased levels of miR‐7 activity, promoted through stimulation by IFNγ from immune cells such as natural killer T‐cells, macrophages, dendritic cells (Koutoulaki et al ., 2010; Robinson et al ., 2010; Nakano et al ., 2012) or from aging fibroblasts themselves, could be the active mechanism in explaining telomerase‐independent senescence of cells. However, the effects of E2 on IFNγ production may alter between cell types, as shown in adherent and nonadherent splenocytes (Nakaya et al ., 2006). Taken together, the findings here showed that regulation of IFNγ and IL6 expression by E2 suggests a broader role for E2 in modulating the immune response.…”

Section: Discussionmentioning

confidence: 99%

17β-estradiol ameliorates age-associated loss of fibroblast function by attenuating IFN-γ/STAT1-dependent miR-7 upregulation

et al. 2016

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SummaryAge‐related defects in fibroblast differentiation and functionality were previously shown to be associated with impaired hyaluronan (HA) synthase 2 (HAS2) and epidermal growth factor receptor (EGFR) function, as a result of upregulated microRNA‐7 (miR‐7) expression. In aging fibroblasts, inhibiting miR‐7 prevented the dysregulation of the HA‐mediated CD44/EGFR signaling pathway. Here, we investigated transcriptional upregulation of miR‐7 and implicated the age‐associated over‐activation of JAK/STAT1 as a primary candidate. STAT1 binding sites were identified on the putative miR‐7 promoter and stimulation of fibroblasts with the inflammatory cytokine, interferon‐γ (IFN‐γ), significantly increased miR‐7 transcriptional activity and resulted in upregulated miR‐7 and loss of EGFR. Additionally, we demonstrated a role for the anti‐inflammatory steroid, 17β‐estradiol (E2), in the attenuation of miR‐7 expression. E2 stimulation promoted estrogen receptor (ER) interactions with the miR‐7 putative promoter and suppressed miR‐7 expression. E2 also attenuated STAT1 expression and activity. Furthermore, treatments with E2 restored fibroblast functionality, including proliferation, migration and differentiation, key events in effective wound healing. In light of our findings, we propose that the regulation of miR‐7 by pro‐ and anti‐inflammatory mediators plays a wider role than previously thought. The modulation of fibroblast functions and ultimately wound healing by miR‐7 activators or inhibitors could provide realistic targets for the restoration of chronic wound healing capabilities in the elderly.

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“…[21][22][23] It has been reported that IL-18 is localized in the dermis in the auricle at 24 hr after the elicitation of CHS with OXA. 34) Our result shows that IL-18 is also localized in the dermis before the elicitation of CHS (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] IL-12 and IL-18 are produced by professional antigen presenting cells, 20) as well as lymphocytes. [21][22][23] The effect of E2 on these chemokines and cytokines has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

17.BETA.-Estradiol Enhances Interleukin-18 mRNA Expression after Sensitization of Mice with Contact Hypersensitivity

Sakazaki

Fujiyama

Ueno

et al. 2009

JOURNAL OF HEALTH SCIENCE

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To clarify the mechanism underlying the enhancing effect of 17β-estradiol (E2) on contact hypersensitivity (CHS) and the expression of interferon (IFN)-γ in mice, the mRNA expression levels of interleukin (IL)-18 were evaluated. Female BALB/c mice aged 3 weeks were ovariectomized, administered 3.2 µg of E2, and sensitized by 50 µl of 3% 4-ethoxymethylene-2-phenyl-2-oxazolin-one (OXA). Seven days later, CHS was elicited by the application of 7.5 µl of 1% OXA on the ear auricles. The auricles, cervical lymph nodes and spleens were excised, and gene expression was evaluated by reverse transcription-polymerase chain reaction. E2 enhanced the expression of IL-18 mRNA in the spleen on the following day and in the ear auricles on days 4 and 7 after sensitization with OXA. The preadministration of an antibody against IL-18 receptor suppressed the CHS and reduced IFN-γ mRNA expression in E2-administered mice. IL-18 was present in the dermis of the ear skin and absent in the epidermis. E2 also enhanced the expression of IFN-γ and IL-18 mRNAs in splenocytes cultured with lipopolysaccharide (LPS). IL-18 protein was detected by flow cytometry in CD4 + , CD8 + and NKG2 + lymphocytes among splenocytes cultured with LPS. These results suggest that E2 enhances lymphocyte activation in the sensitization phase of CHS, and that IFN-γ mRNA expression is enhanced in the elicitation phase of CHS.

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Effect of Estrogens on the Interferon-γ Producing Cell Population of Mouse Splenocytes

Cited by 65 publications

References 34 publications

17β-Estradiol downregulates interferon regulatory factor-1 in murine splenocytes

17β-Estradiol downregulates interferon regulatory factor-1 in murine splenocytes

17β-estradiol ameliorates age-associated loss of fibroblast function by attenuating IFN-γ/STAT1-dependent miR-7 upregulation

17.BETA.-Estradiol Enhances Interleukin-18 mRNA Expression after Sensitization of Mice with Contact Hypersensitivity

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