期刊
EXPERIMENTAL CELL RESEARCH
卷 404, 期 1, 页码 -出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112631
关键词
TIPE2; Inflammatory pain; Inflammation; Rac1/NF-kappa B axis
TIPE2 plays a crucial role in inflammatory pain by suppressing inflammation induced by microglial activation, reducing the activation of the NF-κB pathway, thus alleviating pain and inflammatory responses.
TNF-alpha-inducible protein 8-like 2 (TIPE2) is a recently discovered regulator of inflammation that can maintain immune homeostasis, exerting a significant role in the development of inflammation-related diseases. Here, we aimed to explore the role and potential regulatory mechanism of TIPE2 in the progression of inflammatory pain. In the present study, a mouse BV2 microglia cell activation-mediated inflammatory model was developed with LPS induction, and a mouse inflammatory pain model was established with complete Freund's adjuvant (CFA) injection. In vitro, the TIPE2 expression was decreased in LPS-induced BV2 cells. Overexpression of TIPE2 mitigated LPS-medicated microglial activation via decreasing nitric oxide (NO) generation and the expression of microglia marker IBA-1. Notably, increasing TIPE2 expression alleviated microglial activation-triggered expression levels and releases of proinflammatory factors such as TNF-alpha, IL-1 beta, and IL-6. Mechanism analysis verified that overexpression of TIPE2 blunted Rac1-mediated activation of NF-kappa B pathway following LPS stimulation. More importantly, CFA injection reduced the expression of TIPE2 in a mouse inflammatory pain model and overexpression of TIPE2 alleviated CFA-mediated pain hypersensitivity and inflammatory response, and inactivated microglia cell in vivo. Furthermore, overexpression of TIPE2 decreased Rac1 expression and suppressed the activation of NF-kappa B pathway in spinal cord after CFA injection. In summary, the present study revealed that overexpression of TIPE2 mitigated inflammatory pain through suppressing microglial activation-induced inflammation by inactivating Rac1/NF-kappa B pathway. The study provides a novel theoretical foundation for the therapy of inflammatory pain.
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