Background The six-transmembrane protein of the prostate 2 (STAMP2) is crucial for damage-induced inflammation. Excessive inflammatory responses in microglia have been discovered as the critical factor in triggering neurological diseases. However, inconclusive evidence suggests that STAMP2 alleviates neuroinflammatory diseases by regulating the inflammatory state of microglia. Objectives To ascertain whether the favorable effects of STAMP2 on neuroinflammation act through microglia. Results STAMP2 served as an anti-inflammatory modulator to inhibit the production of inflammatory and reactive oxygen species (ROS) factors and attenuated neurotoxicity. Downregulation of STAMP2 increased the levels of IL-1β, IL-6, ROS, and glutamate, and exogenous STAMP2 knock-in rescued both the exacerbated inflammation and oxidative stress induced by STAMP2 knockdown in BV-2 cells. Mechanistic study showed that STAMP2 siRNA accelerated the expression of p-P65 and p-IkBα, whereas STAMP2OE interrupted the NF-kB translocation. In addition, STAMP2 could reduce neurotoxicity by promoting cell survival and suppressing apoptosis. Conclusion These findings revealed that STAMP2 is involved in regulating the LPS-NF-kB signal pathway to modulate inflammatory processes in microglia cells, which could represent a possible therapeutic therapy for neurodegenerative disorders.
Background The six-transmembrane protein of the prostate 2 (STAMP2) is crucial for damage-induced inflammation. Excessive inflammatory responses in microglia have been discovered as the critical factor in triggering neurological diseases. However, inconclusive evidence suggests that STAMP2 alleviates neuroinflammatory diseases by regulating the inflammatory state of microglia. Objectives To ascertain whether the favorable effects of STAMP2 on neuroinflammation act through microglia. Results STAMP2 served as an anti-inflammatory modulator to inhibit the production of inflammatory and reactive oxygen species (ROS) factors and attenuated neurotoxicity. Downregulation of STAMP2 increased the levels of IL-1β, IL-6, ROS, and glutamate, and exogenous STAMP2 knock-in rescued both the exacerbated inflammation and oxidative stress induced by STAMP2 knockdown in BV-2 cells. Mechanistic study showed that STAMP2 siRNA accelerated the expression of p-P65 and p-IkBα, whereas STAMP2OE interrupted the NF-kB translocation. In addition, STAMP2 could reduce neurotoxicity by promoting cell survival and suppressing apoptosis. Conclusion These findings revealed that STAMP2 is involved in regulating the LPS-NF-kB signal pathway to modulate inflammatory processes in microglia cells, which could represent a possible therapeutic therapy for neurodegenerative disorders.