Alternative Activation of Human Macrophages Is Rescued by Estrogen Treatment In Vitro and Impaired by Menopausal Status

Toniolo, Alice; Fadini, Gian Paolo; Tedesco, Serena; Cappellari, Roberta; Vegeto, Elisabetta; Maggi, Adriana; Avogaro, Angelo; Bolego, Chiara; Cignarella, Andrea

doi:10.1210/jc.2014-2751

Cited by 99 publications

(87 citation statements)

References 41 publications

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“…Importantly, results obtained in the zymosan peritonitis model reveal that these mechanisms are maintained during an acute inflammation of the peritoneum. These results are in agreement with previous studies which suggested that estrogen is involved in macrophage activation and polarization in experimental models of inflammation424344 or in isolated macrophages/cell lines challenged with specific immune stimuli91545. Our study provides a major advancement to this knowledge as it proves estrogen to be per se a physiological regulator of the number and reactivity of peritoneal macrophages in intact healthy animals, in the absence of confounding factors such as recruited circulating monocytes achieved in wound healing or in different models of peritonitis.…”

Section: Discussionsupporting

confidence: 93%

Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge

Pepe

Braga

Renzi

et al. 2017

Sci Rep

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Beyond the physiology of reproduction, estrogen controls the homeostasis of several tissues. Although macrophages play a key role in tissue remodeling, the interplay with estrogen is still ill defined. Using a transcriptomic approach we first obtained a comprehensive list of genes that are differentially expressed in peritoneal macrophages in response to physiological levels of 17β-estradiol (E2) injected in intact female mice. Our data also showed the dynamic nature of the macrophage response to E2 and pointed to specific biological programs induced by the hormone, with cell proliferation, immune response and wound healing being the most prominent functional categories. Indeed, the exogenous administration of E2 and, more importantly, the endogenous hormonal surge proved to support macrophage proliferation in vivo, as shown by cell cycle gene expression, BrdU incorporation and cell number. Furthermore, E2 promoted an anti-inflammatory and pro-resolving macrophage phenotype, which converged on the induction of genes related to macrophage alternative activation and on IL-10 expression in vivo. Hormone action was maintained in an experimental model of peritoneal inflammation based on zymosan injection. These findings highlight a direct effect of estrogen on macrophage expansion and phenotypic adaptation in homeostatic conditions and suggest a role for this interplay in inflammatory pathologies.

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Section: Discussionsupporting

confidence: 93%

Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge

Pepe

Braga

Renzi

et al. 2017

Sci Rep

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“…In vitro treatment of the BV2 microglial cell line with soluble estrogen did not induce an M2 phenotype, but rather reversed and limited the M1 phenotype induced by LPS. These results are similar to the work of Toniolo et al which reported that in vitro treatment with estrogen rescued the M2 phenotype after M1 polarization, but did not increase it over baseline expression (Toniolo et al, 2015). In addition, it was previously reported that the dampening of LPS-stimulated NO production in microglia by estrogen was mediated through estrogen receptor β (ERβ) (Baker et al, 2004).…”

Section: Discussionsupporting

confidence: 91%

Novel feedback loop between M2 macrophages/microglia and regulatory B cells in estrogen-protected EAE mice

Benedek

Zhang

Nguyen

et al. 2017

Journal of Neuroimmunology

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Immunoregulatory sex hormones, including estrogen and estriol, may prevent relapses in multiple sclerosis during pregnancy. Our previous studies have demonstrated that regulatory B cells are crucial for estrogen-mediated protection against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrate an estrogen-dependent induction of alternatively activated (M2) macrophages/microglia that results in an increased frequency of regulatory B cells in the spinal cord of estrogen treated mice with EAE. We further demonstrate that cultured M2-polarized microglia promote the induction of regulatory B cells. Our study suggests that estrogen neuroprotection induces a regulatory feedback loop between M2 macrophages/microglia and regulatory B cells.

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“…NO in saliva may be part of the non-specific natural defense mechanism of the oral cavity against pathogenic bacteria 38. Toniolo et al30 stated that menopause is associated with macrophage activation profiles skewed towards pro-inflammatory phenotype. Macrophages, which play a direct and important function in cell mediated immunity, contain peroxidase, several acid hydrolases and collagenases 39.…”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of Salivary Neopterin Levels and Its Effects to Periodontal Therapy in Pre- and Post-Menopausal Women

et al. 2017

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ObjectivesNeopterin is a valuable diagnostic biomarker, which is elevated in inflammatory conditions like periodontitis, that is characterized by destruction of the supporting structures of the teeth. Among the biomarkers, neopterin occurs in body fluids, and acts as a diagnostic marker for present and future disease activity.MethodsThirty female subjects with chronic periodontitis, mean age 50 years (40-60 years) were included in this study. Depending upon their menstrual history, subjects were categorized into two groups of fifteen each. Group I 15 pre-menopausal women, and Group II 15 post-menopausal women. Saliva was collected, and neopterin levels were assessed by enzyme-linked immunosorbent assay in both the groups, at base line and after three months of nonsurgical periodontal therapy (NSPT). Periodontal parameters like pocket probing depth (PD) and Russell's periodontal disease index (PDI) were assessed before treatment as well as after three months of scaling and root planning.ResultsIntra group analysis showed significant markdown in the mean values of all the parameters from baseline to three months (P < 0.001), for all patients. The intergroup comparison, from baseline to 3 months also showed no significant change in PD and PDI values, but there was a statistically significant difference in the salivary neopterin levels (P = 0.04).ConclusionsNeopterin levels were found to be reduced in three months after NSPT in both the groups, suggesting that the NSPT is the gold standard therapy, and also that neopterin levels in saliva can be used as an indicator to identify periodontal inflammation and destruction.

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Alternative Activation of Human Macrophages Is Rescued by Estrogen Treatment In Vitro and Impaired by Menopausal Status

Cited by 99 publications

References 41 publications

Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge

Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge

Novel feedback loop between M2 macrophages/microglia and regulatory B cells in estrogen-protected EAE mice

Comparative Evaluation of Salivary Neopterin Levels and Its Effects to Periodontal Therapy in Pre- and Post-Menopausal Women

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