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Regulation of Hypoxia-Induced Inflammatory Responses and M1-M2 Phenotype Switch of Primary Rat Microglia by Sex Steroids

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Abstract

Microglia cells are the primary mediators of the CNS immune defense system and crucial for the outcome of shaping inflammatory responses. They are highly dynamic, moving constantly, and become activated by neuronal signaling under pathological conditions. They fulfill a dual role by not only regulating local neuroinflammation but also conferring neuronal protection. Gonadal steroids are known to exert anti-inflammatory effects in the CNS. Recently, we have shown that the microglial-like cell line BV-2 is hypoxia-sensitive and regulated by gonadal steroids. The present study used primary rat cerebral cortex-derived microglia to analyze whether this cell type directly perceive and respond to acute hypoxia. Second, we investigated whether 17β-estradiol (E2) and progesterone (P) interfere with hypoxia-induced changes. Short-term hypoxia increased the expression of a subset of pro-inflammatory (TNFa, IL1b) and oxidative stress-related (Hif1a) genes. The induction of TNFa and IL1b was counteracted by P. Hypoxia shifted the primary microglia to the pro-inflammatory M1 phenotype. The administration of E2 and P favored the neuroprotective M2 phenotype. Our findings extend previous data obtained with BV-2 cells and show that the primary microglia directly perceive hypoxia which increase their inflammatory activity. Both steroid hormones directly and indirectly interact with the microglia cells by reducing the inflammatory scenario and stimulating neuroprotection.

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Authors and Affiliations

  1. Institute of Neuroanatomy, RWTH Aachen University, 52074, Aachen, Germany

    Pardes Habib, Alexander Slowik, Adib Zendedel, Sonja Johann, Jon Dang & Cordian Beyer

  2. Academic Unit of Respiratory Medicine, Department of Infection and Immunity, Faculty of Medicine, University of Sheffield, Sheffield, United Kingdom

    Jon Dang

  3. Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Adib Zendedel

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  1. Pardes Habib
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  2. Alexander Slowik
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  3. Adib Zendedel
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  4. Sonja Johann
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  5. Jon Dang
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  6. Cordian Beyer
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Correspondence to Cordian Beyer.

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Jon Dang and Cordian Beyer contributed equally to this study.

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Habib, P., Slowik, A., Zendedel, A. et al. Regulation of Hypoxia-Induced Inflammatory Responses and M1-M2 Phenotype Switch of Primary Rat Microglia by Sex Steroids. J Mol Neurosci 52, 277–285 (2014). https://doi.org/10.1007/s12031-013-0137-y

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  • DOI: https://doi.org/10.1007/s12031-013-0137-y

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