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Effects of celastrol on BV-2 microglial cells exposed to in vitro hypoxia

Introduction: Microglia are a subset of macrophages permanently present in the central nervous system. Apart from being the key effector of the innate immune response, microglia play a major role in the maintenance of homeostasis. They represent the first line of defense in the central nervous system and as such are affected by all changes in their environment. Microglia respond to hypoxia with acute inflammation, followed by a tendency for an anti-inflammatory switch during the late post-hypoxia period. Celastrol, a naturally occurring quinone methide triterpene derived from the Thunder of God Vine is a pleiotropic compound showing anti-inflammatory, anti-tumor, anti-hypertensive and anti-diabetic activity in numerous cellular and in vivo models. The aim of our research was to determine the effects of celastrol on microglial cells exposed to in vitro hypoxic conditions. Materials and methods: We used murine microglial BV-2 cell line which is commonly used as a substitute for primary microglia. The cells were treated with 100nM of celastrol before or after hypoxia (<0.1% O2, 98% N2), which was induced in a hyperbaric chamber. We analyzed the expression of COX-2, HSP-70 and MHC-1, as respective markers of inflammation, cellular stress and immune response. Measurement of protein expression was performed with Western blot analysis. The measurement was performed in 5 time periods: 0h, 24h, 48h, 72h and 168h post-hypoxia. Results: Hypoxic cells that were not treated with celastrol exhibited increased expression of COX-2, HSP-70 and MHC-1. Treatment with celastrol, both before and after hypoxia, lowered the expression of mentioned markers in all time periods compared to the control. Conclusions: Our results indicate that celastrol acted as anti-inflammatory agent that effectively reduced cellular stress. In addition, celastrols effect on the expression of MHC-1, indicated its possible immunomodulatory potential. Further study is required as celastrol could be used as an anti-inflammatory agent due to the aforementioned effects.

Celastrol, BV-2 microglia, in vitro hypoxia

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