Inhibiting RGS1 attenuates secondary inflammation response and tissue degradation via the TLR/TRIF/NF-κB pathway in macrophage post spinal cord injury.

Dongqian Feng, Jiasheng Yu, Lei Bao, Daobo Fan, Bin Zhang

Neuroscience letters 2022 Jan 18

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Macrophage-dominated inflammation by the activation of Toll-like receptor (TLR) pathway leads to neurological disruption after spinal cord injury (SCI). Regulator of G-protein signaling 1 (RGS1) is reported to be a regulator in inflammation. The present study thus purposes to identify the unknown role of RGS1 mediating TLR on inflammation post SCI. A mouse model of traumatic SCI was established by a mechanical trauma at T10. The mice underwent SCI and a macrophage line activated by lipopolysaccharide (LPS) were treated with shRNA-RGS1 to elucidate the role of RGS1 in inflammatory progression. The inflammatory factors were measured, and the degree of histology and function protection were determined. The expression levels of RGS1, myeloid differentiation primary response protein 88 (Myd88), (TIR-domain-containing adaptor inducing interferon-β (TRIF), p38, metalloproteinase (MMP)-2, and MMP-9 were determined. RGS1 was robustly increased both in LPS-activated macrophage and SCI mice. The TLR signaling pathway-induced inflammation was suppressed by RGS1 knockdown. shRNA-mediated silence of RGS1 was exhibited a prominent decrease in TNF-α, IL-1β and IL-6 via TLR/TRIF/ nuclear factor kappa-B (NF-κB) axis. Depletion of RGS1 also inhibited MMP-induced tissue degradation via MAPK-p38 pathway in SCI mice. Moreover, suppression of RGS1 improved spinal cord histology and function recovery. These findings suggest that RGS1 regulates inflammation and tissue disruption via TLR/TRIF/NF-κB signaling pathway in mice with SCI, thereby explaining a novel target that regulates macrophage inflammation post SCI. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Dongqian Feng, Jiasheng Yu, Lei Bao, Daobo Fan, Bin Zhang. Inhibiting RGS1 attenuates secondary inflammation response and tissue degradation via the TLR/TRIF/NF-κB pathway in macrophage post spinal cord injury. Neuroscience letters. 2022 Jan 18;768:136374