Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage

2007 ◽  
Vol 102 (1) ◽  
pp. 163-168 ◽  
Author(s):  
Takao Suzuki ◽  
Tomoharu Shimizu ◽  
Huang-Ping Yu ◽  
Ya-Ching Hsieh ◽  
Mashkoor A. Choudhry ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Kupffer Cells ◽  
Cytokine Production ◽  
Immune Cell ◽  
Male Rats ◽  
Receptor Subtypes ◽  
Tissue Compartment ◽  
Tnf Α ◽  
17Β Estradiol ◽  
Cell Cytokine Production

Although 17β-estradiol administration following trauma-hemorrhage attenuates plasma cytokines and alteration in immune cell cytokine production, it is not known whether the salutary effects are mediated via estrogen receptor (ER)-α or ER-β. Accordingly, we examined which ER subtype predominantly mediates the salutary effects of 17β-estradiol on systemic inflammatory response/immune cell cytokine production in various tissues following trauma-hemorrhage. Male rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min) and fluid resuscitation. The ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), the ER-β agonist diarylpropionitrile (DPN; 5 μg/kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation, and various measurements were made 24 h thereafter. 17β-Estradiol or PPT administration following trauma-hemorrhage prevented the increase in plasma IL-6 and IL-10 levels that were observed in vehicle-treated animals. IL-6 and TNF-α production by Kupffer cells increased; however, splenic macrophages (SMΦ), alveolar macrophages (AMΦ), and peripheral blood mononuclear cells (PBMC) had decreased release of these cytokines after trauma-hemorrhage. IL-10 production, however, increased in all macrophage populations. Administration of 17β-estradiol following trauma-hemorrhage prevented all of these alterations. PPT had the same effects as 17β-estradiol on IL-6 and TNF-α production by Kupffer cells and SMΦ, and DPN had the same effects on AMΦ and PBMC. The same effects as 17β-estradiol on IL-10 production were observed by PPT on Kupffer cells and DPN on PBMC. Both agonists were equally effective on SMΦ and AMΦ. Thus ER subtypes have tissue compartment-specific roles in mediating the effects of 17β-estradiol on immune cell functions following trauma-hemorrhage.

Salutary effects of 17β-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-α

2007 ◽  
Vol 292 (6) ◽  
pp. C2103-C2111 ◽  
Author(s):  
Takao Suzuki ◽  
Tomoharu Shimizu ◽  
Huang-Ping Yu ◽  
Ya-Ching Hsieh ◽  
Mashkoor A. Choudhry ◽  
...  
Keyword(s):  
T Cells ◽  
Estrogen Receptor ◽  
T Cell ◽  
Signaling Pathways ◽  
Cytokine Production ◽  
Estrogen Receptor Α ◽  
Male Rats ◽  
17Β Estradiol ◽  
Ifn Γ ◽  
Cell Cytokine Production

Although 17β-estradiol (E2) administration following trauma-hemorrhage prevents the suppression in splenocyte cytokine production, it remains unknown whether the salutary effects of 17β-estradiol are mediated via estrogen receptor (ER)-α or ER-β. Moreover, it is unknown which signaling pathways are involved in 17β-estradiol's salutary effects. Utilizing an ER-α- or ER-β-specific agonist, we examined the role of ER-α and ER-β in E2-mediated restoration of T-cell cytokine production following trauma-hemorrhage. Moreover, since MAPK, NF-κB, and activator protein (AP)-1 are known to regulate T-cell cytokine production, we also examined the activation of MAPK, NF-κB, and AP-1. Male rats underwent trauma-hemorrhage (mean arterial pressure 40 mmHg for 90 min) and fluid resuscitation. ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropionitrile (DPN; 5 μg/kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, splenic T cells were isolated, and their IL-2 and IFN-γ production and MAPK, NF-κB, and AP-1 activation were measured. T-cell IL-2 and IFN-γ production was decreased following trauma-hemorrhage, and this was accompanied with a decrease in T-cell MAPK, NF-κB, and AP-1 activation. PPT or 17β-estradiol administration following trauma-hemorrhage normalized those parameters, while DPN administration had no effect. Since PPT, but not DPN, administration following trauma-hemorrhage was as effective as 17β-estradiol in preventing the T-cell suppression, it appears that ER-α plays a predominant role in mediating the salutary effects of 17β-estradiol on T cells following trauma-hemorrhage, and that such effects are likely mediated via normalization of MAPK, NF-κB, and AP-1 signaling pathways.

Estrogen receptor-α predominantly mediates the salutary effects of 17β-estradiol on splenic macrophages following trauma-hemorrhage

2007 ◽  
Vol 293 (3) ◽  
pp. C978-C984 ◽  
Author(s):  
Takao Suzuki ◽  
Tomoharu Shimizu ◽  
Huang-Ping Yu ◽  
Ya-Ching Hsieh ◽  
Mashkoor A. Choudhry ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Signaling Pathways ◽  
Cytokine Production ◽  
Estrogen Receptor Α ◽  
Male Rats ◽  
Splenic Macrophage ◽  
Splenic Macrophages ◽  
Tnf Α ◽  
17Β Estradiol ◽  
Macrophage Cytokine

Although 17β-estradiol administration following trauma-hemorrhage prevents the suppression in splenic macrophage cytokine production, it remains unknown whether the salutary effects are mediated via estrogen receptor (ER)-α or ER-β and which signaling pathways are involved in such 17β-estradiol effects. Utilizing ER-α- or ER-β-specific agonists, this study examined the role of ER-α and ER-β in 17β-estradiol-mediated restoration of macrophage cytokine production following trauma-hemorrhage. In addition, since MAPK and NF-κB are known to regulate macrophage cytokine production, we also examined the activation of those signaling molecules. Male rats underwent trauma-hemorrhage (mean arterial pressure of 40 mmHg for 90 min) and fluid resuscitation. The ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), the ER-β agonist diarylpropionitrile (DPN; 5 μg/kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, splenic macrophages were isolated, and their IL-6 and TNF-α production and activation of MAPK and NF-κB were measured. Macrophage IL-6 and TNF-α production and MAPK activation were decreased, whereas NF-κB activity was increased, following trauma-hemorrhage. PPT or 17β-estradiol administration after trauma-hemorrhage normalized those parameters. DPN administration, on the other hand, did not normalize the above parameters. Since PPT but not DPN administration following trauma-hemorrhage was as effective as 17β-estradiol in preventing the suppression in macrophage cytokine production, it appears that ER-α plays the predominant role in mediating the salutary effects of 17β-estradiol on macrophage cytokine production following trauma-hemorrhage and that such effects are likely mediated via normalization of MAPK but not NF-κB signaling pathways.

scholarly journals Estrogen Receptor Signaling and Its Relationship to Cytokines in Systemic Lupus Erythematosus

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
E. Kassi ◽  
P. Moutsatsou
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Estrogen Receptor ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Receptor Protein ◽  
Receptor Subtypes ◽  
Receptor Signaling ◽  
Systemic Lupus ◽  
Estrogen Receptor Signaling

Dysregulation of cytokines is among the main abnormalities in Systemic Lupus Erythematosus (SLE). However, although, estrogens, which are known to be involved in lupus disease, influence cytokine production, the underlying molecular mechanisms remain poorly defined. Recent evidence demonstrates the presence of estrogen receptor in various cell types of the immune system, while divergent effects of estrogens on the cytokine regulation are thought to be implicated. In this paper, we provide an overview of the current knowledge as to how estrogen-induced modulation of cytokine production in SLE is mediated by the estrogen receptor while simultaneously clarifying various aspects of estrogen receptor signaling in this disease. The estrogen receptor subtypes, their structure, and the mode of action of estrogens by gene activation and via extranuclear effects are briefly presented. Results regarding the possible correlation between estrogen receptor gene polymorphisms and quantitative changes in the receptor protein to SLE pathology and cytokine production are reviewed.

scholarly journals Ginseng Berry Extract Rich in Phenolic Compounds Attenuates Oxidative Stress but not Cardiac Remodeling post Myocardial Infarction

2019 ◽  
Vol 20 (4) ◽  
pp. 983 ◽  
Author(s):  
Mihir Parikh ◽  
Pema Raj ◽  
Liping Yu ◽  
Jo-Ann Stebbing ◽  
Suvira Prashar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
T Cell ◽  
Phenolic Compounds ◽  
Cytokine Production ◽  
T Cell Subsets ◽  
Male Rats ◽  
Ginseng Root ◽  
Rat Hearts ◽  
Tnf Α

The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI). Coronary artery ligation was performed on Sprague–Dawley male rats to induce MI after which animals were randomized into groups receiving either distilled water or GBE intragastrically for 8 weeks. Echocardiography and assays for malondialdehyde (MDA) and TNF-α were conducted. Flow cytometry was used to test the effects of GBE on T cell phenotypes and cytokine production. Although GBE did not improve the cardiac functional parameters, it significantly attenuated oxidative stress in post-MI rat hearts. GBE treatment also resulted in lower than control levels of TNF-α in post-MI rat hearts indicating a strong neutralizing effect of GBE on this cytokine. However, there was no effect of GBE on the proportion of different T cell subsets or ex-vivo cytokine production. Taken together, the present study demonstrates GBE reduces oxidative stress, however no effect on cardiac structure and function in post-MI rats. Moreover, reduction of TNF-α levels below baseline raises concern regarding its use as prophylactic or preventive adjunct therapy in cardiovascular disease.

scholarly journals Reduced vasorelaxation to estradiol and G-1 in aged female and adult male rats is associated with GPR30 downregulation

2013 ◽  
Vol 305 (1) ◽  
pp. E113-E118 ◽  
Author(s):  
Sarah H. Lindsey ◽  
Ariel S. da Silva ◽  
Mauro S. Silva ◽  
Mark C. Chappell
Keyword(s):  
Blood Pressure ◽  
Estrogen Receptor ◽  
Receptor Expression ◽  
Mesenteric Arteries ◽  
Male Rats ◽  
Resistance Arteries ◽  
Intact Male ◽  
Blood Pressure Lowering Effect ◽  
Nitric Oxide Synthase Inhibitor ◽  
17Β Estradiol

Previously, we reported that chronic activation of the estrogen receptor GPR30 by its selective agonist G-1 decreases blood pressure in ovariectomized hypertensive mRen2.Lewis (mRen2) rats but not intact male littermates. Furthermore, G-1 relaxes female mesenteric resistance arteries via both endothelium-dependent and -independent mechanisms. Because of the lack of a blood pressure-lowering effect by G-1 in males and the potential influence of aging on estrogen receptor expression, we hypothesized that GPR30-dependent vasodilation and receptor expression are altered in males and aged females. Thus, we assessed the response to 17β-estradiol or G-1 in mesenteric arteries obtained from 15-wk-old normotensive Lewis and hypertensive mRen2 females and males as well as 52-wk-old Lewis females. Vasodilation to 17β-estradiol (E2) and G-1 was significantly attenuated in 15-wk-old Lewis and mRen2 males compared with age-matched females. Pretreatment of male vessels with the nitric oxide synthase inhibitor l-NAME had no significant effect on the estradiol or G-1 response. In aged females, E2 and G-1 vasorelaxation was also significantly blunted; however, l-NAME essentially abolished the response. Associated with the reduced vascular responses, GPR30 expression in mesenteric arteries was approximately 50% lower in males and aged females compared with young females. We conclude that alterations in GPR30 expression and signaling may contribute to vascular dysfunction in aging females and a greater blood pressure in hypertensive males.

Upregulation of estrogen receptor α and mediation of 17β-estradiol vasoprotective effects via estrogen receptor α in basilar arteries in rats after experimental subarachnoid hemorrhage

2008 ◽  
Vol 109 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Huei-Chuan Shih ◽  
Chih-Lung Lin ◽  
Shu-Chuan Wu ◽  
Aij-Lie Kwan ◽  
Yi-Ren Hong ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Estrogen Receptor ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Estrogen Receptor Α ◽  
Male Rats ◽  
Enos Expression ◽  
Basilar Arteries ◽  
17Β Estradiol ◽  
Oxide Synthase

Object The authors previously demonstrated that 17β-estradiol benzoate (E2) treatment prevents subarachnoid hemorrhage (SAH)–induced cerebral vasospasm and preserves endothelial nitric oxide synthase (eNOS) in male rats. Changes in the expression of estrogen receptor (ER) subtypes ERα and -β and their roles in the E2-mediated preservation of eNOS in SAH remain unknown. In the present study the effects of SAH on the expression of ERα and -β in the cerebral arteries were clarified, and the receptor roles in the E2-mediated preservation of eNOS expression in SAH were differentiated. Methods A 2-hemorrhage SAH model was induced by 2 autologous blood injections into the cisterna magna of adult male rats. The effect of SAH on ERα and -β expression was evaluated. Other rats subcutaneously received implanted Silastic tubes containing corn oil with E2 and daily injections of various doses of an ERα- (methyl-piperidinopyrazole [MPP]) or ERβ-selective antagonist (R,R-tetrahydrochrysene) after the first hemorrhage. The protein levels of ERα, ERβ, eNOS, and inducible nitric oxide synthase (iNOS) from basilar arteries were examined using Western blot analysis, and their mRNAs were evaluated by reverse transcription–polymerase chain reaction. Results The ERα but not the ERβ was upregulated in the basilar artery after SAH. Treatment with MPP eliminated E2-mediated effects in SAH, relieved cerebral vasospasm, preserved eNOS expression, and suppressed iNOS expression. Conclusions Estrogen receptor α is upregulated in the basilar artery after SAH. Note that E2 exerts its protective effects through ERα-dependent pathways to relieve cerebral vasospasm and preserve eNOS expression. A selective ERα agonist may be the drug of choice for the treatment of patients with SAH.

Role of PPARγ in the salutary effects of 17β-estradiol on kupffer cell cytokine production following trauma-hemorrhage

2010 ◽  
Vol 226 (1) ◽  
pp. 205-211 ◽  
Author(s):  
Takao Suzuki ◽  
Takashi Kawasaki ◽  
Mashkoor A. Choudhry ◽  
Irshad H. Chaudry
Keyword(s):  
Kupffer Cell ◽  
Cytokine Production ◽  
17Β Estradiol ◽  
Cell Cytokine Production

Relation of HLA-B27, Tumor Necrosis Factor-α Promoter Gene Polymorphisms, and T Cell Cytokine Production in Ankylosing Spondylitis — A Comprehensive Genotype-Phenotype Analysis from an Observational Cohort

2011 ◽  
Vol 38 (11) ◽  
pp. 2436-2441 ◽  
Author(s):  
DENIS A. PODDUBNYY ◽  
ELISABETH MÄRKER-HERMANN ◽  
WIEBKE KALUZA-SCHILLING ◽  
HENNING ZEIDLER ◽  
JURGEN BRAUN ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Hla B27 ◽  
Tnf Α ◽  
Promoter Gene ◽  
Clinical Measurements ◽  
Factor Α ◽  
Necrosis Factor ◽  
Cell Cytokine Production

Objective.In a pilot study, a distinct T cell cytokine pattern associated with HLA-B27 status and a tumor necrosis factor-α (TNF-α) promoter gene polymorphism was found at –308 (TNF–308). The objective of our study was to assess these associations in a different cohort of patients with ankylosing spondylitis (AS) and to evaluate any effect on clinical measurements.Methods.Peripheral T cell cytokine production of patients with AS (n = 121) from the German Spondyloarthritis Inception Cohort was assessed by flow cytometry and correlated with HLA-B27, TNF–238, and TNF–308, and with clinical measurements.Results.In HLA-B27-positive, anti-TNF-naive patients with AS, the percentages of TNF-α-producing (5.02%) and interleukin 10-producing (0.31%) CD8+ cells were significantly lower in comparison to HLA-B27-negative patients (9.52%, p = 0.048, and 0.46%, p = 0.037, respectively). A nonsignificant trend was found for a lower production of TNF-α by CD4+ and interferon-γ by both CD4+ and CD8+ T cells, as compared to HLA-B27-negative patients with AS (p > 0.05 for all comparisons). The A allele at TNF–308 was associated with a lower percentage of TNF-α-producing CD4+ T cells. No significant correlations were found between clinical or radiological measurements and cytokine production or with TNF-α promoter gene polymorphisms.Conclusion.Modulation of T cell cytokines by HLA-B27 might play a role in AS pathogenesis in B27-positive individuals. No conclusive data were obtained for the TNF–308 polymorphism on cytokine production, and no effect of cytokines or genetic polymorphisms on clinical manifestations was observed.

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