Department of Endodontics, Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, No. 143, Dongzong Road, Pingshan District, Shenzhen, 518118, China.
School of Stomatology, Southern Medical University, Guangzhou, China.
Inflammation. 2023 Jun;46(3):876-891. doi: 10.1007/s10753-022-01777-z. Epub 2023 Jan 4.
Macrophages actively participate in immunomodulatory processes throughout periodontal inflammation. Regulation of M1/M2 polarization affects macrophage chemokine and cytokine secretion, resulting in a distinct immunological status that influences prognosis. Semaphorin 3A (Sema3A), a neurite growth factor, exerts anti-inflammatory effects. In this study, we investigated the immunomodulation of Sema3A on macrophage-related immune responses in vivo and in vitro. Topical medications of Sema3A in mice with periodontitis alleviated inflammatory cell infiltration into gingival tissue and reduced areas with positive IL-6 and TNFα expression. We observed that the positive area with the M2 macrophage marker CD206 increased and that of the M1 macrophage marker iNOS decreased in Sema3A-treated mice. It has been postulated that Sema3A alleviates periodontitis by regulating alternative macrophage activation. To understand the mechanism underlying Sema3A modulation of macrophage polarization, an in vitro macrophage research model was established with RAW264.7 cells, and we demonstrated that Sema3A promotes LPS/IFNγ-induced M1 macrophages to polarize into M2 macrophages and activates the PI3K/AKT/mTOR signaling pathways. Inhibition of the PI3K signaling pathway activation might reduce anti-inflammatory activity and boost the expression of the inflammatory cytokines, iNOS, IL-12, TNFα, and IL-6. This study indicated that Sema3A might be a feasible drug to regulate alternative macrophage activation in the inflammatory response and thus alleviate periodontitis.
巨噬细胞在牙周炎炎症过程中积极参与免疫调节。M1/M2 极化的调节影响巨噬细胞趋化因子和细胞因子的分泌，导致不同的免疫状态，从而影响预后。神经丝蛋白 3A（Sema3A）是一种神经突生长因子，具有抗炎作用。在本研究中，我们研究了 Sema3A 对体内和体外巨噬细胞相关免疫反应的免疫调节作用。牙周炎小鼠局部应用 Sema3A 可减轻炎症细胞浸润到牙龈组织，并减少 IL-6 和 TNFα 表达阳性的区域。我们观察到 Sema3A 处理组小鼠的 M2 巨噬细胞标志物 CD206 阳性面积增加，M1 巨噬细胞标志物 iNOS 减少。有人假设 Sema3A 通过调节替代型巨噬细胞激活来缓解牙周炎。为了了解 Sema3A 调节巨噬细胞极化的机制，我们在 RAW264.7 细胞中建立了体外巨噬细胞研究模型，结果表明 Sema3A 促进 LPS/IFNγ 诱导的 M1 巨噬细胞向 M2 巨噬细胞极化，并激活 PI3K/AKT/mTOR 信号通路。抑制 PI3K 信号通路的激活可能会降低抗炎活性并增加炎症细胞因子 iNOS、IL-12、TNFα 和 IL-6 的表达。本研究表明，Sema3A 可能是一种调节炎症反应中替代型巨噬细胞激活的可行药物，从而缓解牙周炎。
