Expression of estrogen receptor subtypes and neuronal nitric oxide synthase in neutrophils from women and men Regulation by estrogen

Molero, Laura; Garcı́a-Durán, Margarita; Díaz-Recasens, J.; Rico, Luís; Casado, Santos; López‐Farré, Antonio

doi:10.1016/s0008-6363(02)00505-9

Cited by 107 publications

(60 citation statements)

References 43 publications

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“…Treatment of either humans or mice with E2 increases numbers of neutrophils in the blood and lungs, respectively (50,51). Neutrophils possess both ER␣ and ER␤ (52,53). Functionally, in vitro exposure of neutrophils to E2 (i) increases degranulation, elastase release, and production of reactive oxygen species, (ii) inhibits caspase 3/9 and delays apoptosis, and (iii) increases cell adhesion molecules and interactions with endothelial cells (54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol Protects Females against Influenza by Recruiting Neutrophils and Increasing Virus-Specific CD8 T Cell Responses in the Lungs

Robinson

Hall

Nilles

et al. 2014

J Virol

157

145

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ABSTRACT17␤-Estradiol (E2) treatment limits the pathology associated with pulmonary diseases caused by pathogens, allergens, and asthma, partly by reducing the production of proinflammatory cytokines and chemokines. To test the hypothesis that E2 protects against influenza A virus (IAV) infection by altering the recruitment and activity of innate immune cells and T cells, chemokine concentrations were measured and innate and adaptive immune cells were enumerated from the lungs of E2-and placebotreated ovariectomized female C57BL/6 mice following infection. Females treated with E2 experienced less morbidity but had similar lung virus titers to placebo-treated females. Females treated with E2 had lower induction of CCL2 but higher CCL3 and CXCL1 responses in their lungs than placebo-treated females. Pulmonary recruitment of neutrophils, NK cells, macrophages, and dendritic cells was increased following infection, but only neutrophil numbers were greater in E2-treated than placebotreated females. Neutrophils enhance the responses of influenza virus-specific CD8 T cells to promote virus clearance and improve the outcome of infection. Total numbers of virus-specific CD8 T cells were not altered by treatment with E2, but the proportion of gamma interferon (IFN-␥)-and tumor necrosis factor alpha (TNF-␣)-producing, virus-specific CD8 T cells was increased. Neutrophil depletion in E2-treated females increased morbidity, reduced pulmonary production of chemoattractants for neutrophils, and reduced IFN-␥ production by virus-specific CD8 T cells. Neutrophils mediate both inflammation and tissue repair during IAV infection and are regulated by E2 to improve the outcome of influenza in females. IMPORTANCESevere influenza is associated with excessive inflammation that leads to tissue damage. We demonstrate that estradiol (E2) is a potent anti-inflammatory hormone that reduces the severity of influenza A virus infection in females. Treatment of female C57BL/6 mice with E2 does not affect virus replication but rather alters the production of chemokines, pulmonary recruitment of neutrophils, and the cytokine responses of virus-specific CD8 T cells to protect females against severe influenza.

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Section: Discussionmentioning

confidence: 99%

17β-Estradiol Protects Females against Influenza by Recruiting Neutrophils and Increasing Virus-Specific CD8 T Cell Responses in the Lungs

Robinson

Hall

Nilles

et al. 2014

J Virol

157

145

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“…Neutrophils are recruited into the tissue by local production of cytokines and then contribute to tissue destruction by the production of reactive oxygen metabolites, granule enzymes, and cytokines that further amplify the inflammatory response by acting on macrophages and lymphocytes (Kadl and Leitinger, 2005). Neutrophils were shown to express GR and ER receptor, suggesting a potential role of these receptors in the regulation of neutrophil function (Molero et al, 2002). Other studies have also demonstrated that GR may modulate leukocyte-endothelial cell interactions during inflammation through regulation of endothelial adhesion molecules (Schramm and Thorlacius, 2004).…”

Section: Cross-talk Between Gr and Er In A Model Of Inflammation 139mentioning

confidence: 99%

Estrogen Receptor Antagonist Fulvestrant (ICI 182,780) Inhibits the Anti-Inflammatory Effect of Glucocorticoids

Cuzzocrea¹,

Bruscoli²,

Crisafulli³

et al. 2006

Mol Pharmacol

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The glucocorticoid receptor (GR) and estrogen receptor (ER) play important roles in both physiological and pathological conditions involving cell growth and differentiation, lipolysis, control of glucose metabolism, immunity, and inflammation. In fact, recent studies suggest that 17␤-estradiol, like glucocorticoids, may also have anti-inflammatory properties, even if the molecular mechanisms responsible for these activities have not yet been completely clarified. The present study was designed to gain a better understanding of the possible cross-talk between GR and ER in a model of lung inflammation (carrageenan-induced pleurisy). In particular, we have investigated whether fulvestrant (ICI 182,780), a selective ER-␣ antagonist, is able to attenuate the well known anti-inflammatory effect of dexamethasone (DEX), a synthetic glucocorticoid, in ovariectomized rats. We show that ICI 182,780, a selective ER-␣ antagonist, reverses the anti-inflammatory activity exhibited by DEX. Moreover, the coadministration of ICI 182,780 significantly inhibited the ability of DEX to reduce: 1) the degree of lung injury, 2) the rise in myeloperoxidase activity, 3) the increase of poly-(ADP-ribose) polymerase activity, tumor necrosis factor ␣, and interleukin-1␤ levels, 4) inducible nitric-oxide synthase, 5) lipid peroxidation, 6) nitrotyrosine formation, 7) cyclooxygenase expression, and 8) the IB-␣ degradation caused by carrageenan administration. In addition, quantitative PCR shows that DEX down-regulates GR and up-regulates glucocorticoid-induced leucine zipper levels, whereas ICI 182,780 does not counteract these effects. In conclusion, these results suggest that the in vivo anti-inflammatory property of DEX is also related to the ER-␣.The immune and inflammatory responses are complex physiological processes that are critically important to the homeostasis and ultimate survival of an organism. Their coordinate regulation must be assured to allow appropriate and timely immune reaction without an over-reaction that might cause damage to the host. The inflammatory process is invariably characterized by a production of prostaglandins, leukotrienes, histamine, bradykinin, platelet-activating factor and by a release of chemicals from tissues and migrating cells (Vane and Botting, 1987). Carrageenan-induced local inflammation is commonly used to evaluate the efficacy of nonsteroidal anti-inflammatory drugs. Therefore, carrageenan-induced local inflammation (pleurisy) is a useful model to assess the contribution of mediators involved in vascular changes associated with acute inflammation. In particular, the initial phase of acute inflammation (0 -1 h), which is not inhibited by nonsteroidal anti-inflammatory drugs such us indomethacin or aspirin, has been attributed to the release of histamine, 5-hydroxytryptamine, and bradykinin, followed S.C. and S.B. contributed equally to this work. Article, publication date, and citation information can be found at

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“…The effects of E 2 , PPT, and DPN on estrogen-mediated immunomodulation were investigated in ovariectomized (ovx) mice, PPT but not DPN showed effects on thymus (Li & McMurray 2006). Both ER subtypes have been found in different leukocyte populations in human tissues and in peripheral blood (Stygar et al 2001, 2006, Molero et al 2002. Still, the functional activity and importance of ERs in blood cells are principally unknown.…”

Section: Introductionmentioning

confidence: 99%

Studies on estrogen receptor (ER) α and β responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists

Stygar¹,

Masironi²,

Eriksson³

et al. 2007

Journal of Endocrinology

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Major reproductive events such as menstruation, ovulation, implantation, and cervical ripening are characterized by an increased number of invading leukocytes in the tissues. Sex steroid hormones, particularly estrogens, play an important role in these dynamic changes in the female reproductive tract. Estrogens have also been implicated in the pathogenesis of many common pathological conditions associated with leukocyte infiltration and immunological dysfunction, such as autoimmune diseases and atherosclerosis. Although the two estrogen receptor (ER) subtypes, ERa and ERb, have been found in different leukocyte populations in tissues and in peripheral blood, there is still very little known about functional activity and importance of ERs in blood cells. To elucidate the different roles for ERa and ERb in peripheral blood leukocytes, we used microarray gene expression profiling of rat peripheral blood leukocytes subjected to in vivo treatment with estradiol (E 2 ), the selective ERa agonist 4,4 0 ,4 00 -(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), and the selective ERb agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). We report the identification of genes that were commonly regulated by E 2 , PPT, and DPN, and genes that were regulated either by the ERa or ERb agonist. Further confirmatory analyses of the selected regulated genes 12-lipoxygenase, fibulin-1, furin, and calgranulin B are also presented. These results were then compared with those from the uterine tissue of the same animals. Our study demonstrates that peripheral blood leukocytes are responsive to estrogens. E 2 and selective ERa and ERb agonists regulate a number of genes that may contribute to inflammation and remodeling of the extracellular matrix.

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Expression of estrogen receptor subtypes and neuronal nitric oxide synthase in neutrophils from women and men Regulation by estrogen

Cited by 107 publications

References 43 publications

17β-Estradiol Protects Females against Influenza by Recruiting Neutrophils and Increasing Virus-Specific CD8 T Cell Responses in the Lungs

17β-Estradiol Protects Females against Influenza by Recruiting Neutrophils and Increasing Virus-Specific CD8 T Cell Responses in the Lungs

Estrogen Receptor Antagonist Fulvestrant (ICI 182,780) Inhibits the Anti-Inflammatory Effect of Glucocorticoids

Studies on estrogen receptor (ER) α and β responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists

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