Abstract
It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. Herein, using LPS to establish acute inflammation model of mouse liver and cell line inflammation model, we investigated whether miR-155/GSK-3β regulated NF-κB signaling pathway, and CsIVa exerted anti-inflammatory effects by regulating miR-155/GSK-3β signaling pathway. Our results showed that LPS induced high expression of miR-155 and miR-155 promoted macrophage activation through GSK-3β. In addition, CsIVa inhibited inflammatory responses in LPS-induced mouse liver and RAW264.7 cells. Furthermore, we demonstrated that CsIVa improved the inflammatory response in LPS-induced RAW264.7 cells by inhibiting miR-155, increasing GSK-3β expression, and inhibiting NF-κB signaling pathway. In conclusion, our study reveals that CsIVa suppresses LPS-triggered immune response by miR-155/GSK-3β-NF-κB signaling pathway.
Highlights
It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities
It has been recognized that LPS increased the expression of NO, IL-1β, and tumor necrosis factor (TNF)-α in RAW264.7 cells
Our results showed that miR-155 exerted an inhibitory effect on GSK-3β activity and elevated the expression of miR-155, iNOS, TNF-α, and IL-1β in a dose-dependent manner in RAW264.7 cells, suggesting that miR-155 promotes the macrophage activation and suppress GSK-3β expression (Fig. 2a,b)
Summary
It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. MiR-155,an important member of the miRNA family, is a well-known immunomodulatory miRNA that can be induced by LPS and control inflammatory processes in multiple cells and organs[9,10,11,12] These data suggest that miR-155 plays critical roles in regulating the inflammatory response through controlling lymphocytes and mediates the expression of related proteins. The effect of GSK-3β on inflammation is partly due to its ability to regulate the NF-κB signaling pathway[13,14].Studies confirm that miR-155 is involved in cell proliferation and apoptosis by inhibiting the expression of GSK-3β15,16 All of these studies hint us that miR-155 may play critical roles in affecting the activation of macrophages through GSK-3β and NF-κB signaling pathways. To find out the agents that can selectively regulate miR-155/GSK-3β-NF-κB signaling pathway will be highly significant for prevention and treatment of inflammation-related diseases
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