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SERMs Promote Anti-Inflammatory Signaling and Phenotype of CD14+ Cells.

ABSTRACT: Signaling via estrogen receptors (ER) is recognized as an essential part of the immune regulation, and ER-mediated signaling is involved in autoimmune reactions. Especially ER? activation in immune cells has been suggested to skew cytokine production toward Th2/M2-type mediators, which can have protective effect on inflammatory diseases and reduce Th1 and Th17 responses. These effects are caused by increased alternative activation of macrophages and changes in the activation of different T cell populations. In humans, hormonal status has been shown to have a major impact on several inflammatory diseases. Selective estrogen receptor modulators (SERMs) are ER ligands that regulate ER actions in a tissue-specific manner mostly lacking the adverse effects of steroid hormones. The impact of SERMs on the immune system is less studied, but it is suggested that certain SERMs may also produce immunoprotective effects. Here, we show that two novel SERMs and raloxifene affect immune cells by promoting M2 macrophage phenotype, alleviating NF?B activity, inhibiting T cell proliferation, and stimulating the production of anti-inflammatory compounds such as IL10 and IL1 receptor antagonist. Thus, these compounds have high potency as drug candidates against autoimmune diseases.

SUBMITTER: Polari L

PROVIDER: S-EPMC6061028 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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SERMs Promote Anti-Inflammatory Signaling and Phenotype of CD14+ Cells.

Polari Lauri L Wiklund Anu A Sousa Sofia S Kangas Lauri L Linnanen Tero T Härkönen Pirkko P Määttä Jorma J

Inflammation 20180801 4

Signaling via estrogen receptors (ER) is recognized as an essential part of the immune regulation, and ER-mediated signaling is involved in autoimmune reactions. Especially ERα activation in immune cells has been suggested to skew cytokine production toward Th2/M2-type mediators, which can have protective effect on inflammatory diseases and reduce Th1 and Th17 responses. These effects are caused by increased alternative activation of macrophages and changes in the activation of different T cell ...[more]

PMID: 29574654

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SERMs Promote Anti-Inflammatory Signaling and Phenotype of CD14+ Cells.

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SERMs Promote Anti-Inflammatory Signaling and Phenotype of CD14+ Cells.

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