Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C

Yuan, Ying; Shimizu, Ichiro; Shen, Mi; Aoyagi, Eriko; Takenaka, Hidetaka; Itagaki, Tatuzo; Urata, Mari; Sannomiya, Katsutaka; Kohno, Nao; Tamaki, Katsuyoshi; Shono, Masayuki; Takayama, Tetsuji

doi:10.3748/wjg.14.2200

Cited by 40 publications

(31 citation statements)

References 30 publications

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“…Yet, estradiol and progesterone can have either immunostimulant or immunosuppressive effects (6,7,21,37,47). Possible explanations for the observed differences include factors such as the concentration, timing and duration of hormone treatment, and expression of specific receptor subtypes and receptor coactivators in distinct cell types of different species (2,6,13,38,39).…”

Section: Discussionmentioning

confidence: 99%

“…After birth, estradiol and progesterone blood levels decrease within less than 1 week to 0.1 nM and 5 nM, respectively, which corresponds to levels observed in adult males. Whereas estradiol has been shown to inhibit cytokine production by adult PBMCs, the effect of progesterone on adult immune cells is less clear (3,13,47). To evaluate the developmental response of immune cells to steroids, PBMCs from adult males and premenopausal females were preincubated for 16 h with estradiol (10 Ϫ7 to 10 Ϫ9 M) or progesterone (10 Ϫ5 to 10 Ϫ7 M) prior to stimulation with E. coli ( Fig.…”

Section: Estradiol and Progesterone Inhibit Cytokine Production Bymentioning

confidence: 99%

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Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns

et al. 2011

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Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-B pathway but not the mitogenactivated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period.Newborns are at high risk of severe bacterial infections. Early-onset neonatal sepsis occurs during the first week of life in 1 to 5 per 1,000 births (14,24,25). Group B Streptococcus (GBS) and Escherichia coli are involved in more than 50% of episodes of early-onset neonatal sepsis. Despite antimicrobial therapy and improvements in neonatal intensive care, the mortality due to neonatal sepsis remains high (5 to 15%) and survivors are at risk of permanent neurologic damage (14,24,25). The particularly high susceptibility to infection during the neonatal period has been associated with quantitative and qualitative deficiencies of innate immunity (such as reduced levels of opsonins, decreased cytokine production, and impaired function of phagocytes) and adaptive immunity (such as impaired function of antigen-presenting cells and T cells and decreased production of immunoglobulins) (1,19,36). Although the differences between the neonatal and adult immune responses are relatively well described, the underlying mechanisms that account for the decreased ability of newborns to mount efficient immune responses remain largely unknown.Fetuses are chronically exposed to high levels of steroid hormones due to placental production. Concentrations ...

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Section: Discussionmentioning

confidence: 99%

Section: Estradiol and Progesterone Inhibit Cytokine Production Bymentioning

confidence: 99%

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns

et al. 2011

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“…For instance, an in vivo study showed that transdermal estrogen therapy reduces circulating levels of several cytokines, including MCP-1 (Yasui et al 2009). In parallel, studies in vitro demonstrate that estrogen reduces MCP-1 production in several cells, such as peripheral blood mononuclear cells and immature dendritic cells (Bengtsson et al 2004, Yuan et al 2008). The present study provides the first evidence that estrogen directly acts on VSMCs by decreasing LPS-stimulated MCP-1 production, which adds new insight into estrogen's anti-inflammatory functions in cardiovascular system.…”

Section: Discussionmentioning

confidence: 99%

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Jiang¹,

Xu²,

Zheng³

et al. 2010

Journal of Molecular Endocrinology

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Atherosclerosis is an inflammatory disease where lipopolysaccharide (LPS) triggers the release of inflammatory cytokines that accelerate its initiation and progression. Estrogen has been proven to be vasoprotective against atherosclerosis; however, the anti-inflammatory function of estrogen in the vascular system remains obscure. In this study, we investigated the effect of estrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1; listed as CCL2 in the MGI database) production in vascular smooth muscle cells (VSMCs). LPS significantly enhances MCP-1 production and this is dependent on nuclear factor k B (NFkB) signaling, since the use of NFkB inhibitor pyrrolidine dithiocarbamate or the silencing of NFkB subunit p65 expression with specific siRNA largely impairs LPS-enhanced MCP-1 production. On the contrary, 17b-estradiol (E 2 ) inhibits LPS-induced MCP-1 production in a time-and dosedependent manner, which is related to the suppression of p65 translocation to nucleus. Furthermore, p38 MAPK is rapidly activated in response to LPS, while E 2 markedly inhibits p38 MAPK activation. Transfection with p38 MAPK siRNA or the use of p38 MAPK inhibitor SB203580 markedly attenuates LPS-stimulated p65 translocation to nucleus and MCP-1 production, suggesting that E 2 suppresses NFkB signaling by the inactivation of p38 MAPK signaling. LPS promotes VSMCs migration and this is abrogated by MCP-1 antibody, implying that MCP-1 may play a major role as an autocrine factor in atherosclerosis. In addition, E 2 inhibits LPS-promoted cell migration by downregulation of MCP-1 production.Overall, our results demonstrate that E 2 exerts anti-inflammatory property antagonistic to LPS in VSMCs by reducing MCP-1 production, and this effect is related to the inhibition of p38 MAPK/NFkB cascade.

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“…Mouse peritoneal macrophages express receptors for both estradiol (both the alpha and beta isoforms) and progesterone (Huang et al, 2008), and are responsive to these hormones in vitro. Progesterone promotes the expression of proinflammatory cytokines, including tumour necrosis factor alpha (TNF), CCL2 (also known as monocyte chemoattractant protein 1) and interleukin 1 beta (IL1), by mouse and human macrophages, whereas estradiol suppresses expression (FrazierJessen and Kovacs, 1995;Huang et al, 2008;Yuan et al, 2008). Alternatively, indirect hormonal regulation might be mediated by the epithelium.…”

Section: Hormonal Regulation Of Macrophage Functionmentioning

confidence: 99%

Dual roles for macrophages in ovarian cycle-associated development and remodelling of the mammary gland epithelium

et al. 2010

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SUMMARYEach ovarian cycle, the mammary gland epithelium rotates through a sequence of hormonally regulated cell proliferation, differentiation and apoptosis. These studies investigate the role of macrophages in this cellular turnover. Macrophage populations and their spatial distribution were found to fluctuate across the cycle. The number of macrophages was highest at diestrus, and the greatest number of macrophages in direct contact with epithelial cells occurred at proestrus. The physiological necessity of macrophages in mammary gland morphogenesis during the estrous cycle was demonstrated in Cd11b-Dtr transgenic mice. Ovariectomised mice were treated with estradiol and progesterone to stimulate alveolar development, and with the progesterone receptor antagonist mifepristone to induce regression of the newly formed alveolar buds. Macrophage depletion during alveolar development resulted in a reduction in both ductal epithelial cell proliferation and the number of alveolar buds. Macrophage depletion during alveolar regression resulted in an increased number of branch points and an accumulation of TUNEL-positive cells. These studies show that macrophages have two roles in the cellular turnover of epithelial cells in the cycling mammary gland; following ovulation, they promote the development of alveolar buds in preparation for possible pregnancy, and they remodel the tissue back to its basic architecture in preparation for a new estrous cycle.

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Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C

Abstract: These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production, whereas progesterone may counteract the favorable E2 effects.

Cited by 40 publications

References 30 publications

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns

17β-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells

Dual roles for macrophages in ovarian cycle-associated development and remodelling of the mammary gland epithelium

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