Department of Immunology, Medical College of Qingdao University, Qingdao, Shandong 266071, PR China.
Department of Special Medicine, School of Basic Medical College, Qingdao University, Qingdao, Shandong 266071, PR China.
Int Immunopharmacol. 2023 Jul;120:110330. doi: 10.1016/j.intimp.2023.110330. Epub 2023 May 27.
The C-X-C chemokine ligand (CXCL) 1 and its receptor C-X-C chemokine receptor (CXCR) 2 are widely expressed in the peripheral nervous systems (PNS) and central nervous systems (CNS) and are involved in the development of inflammation and pain after various nerve injuries. Once a nerve is damaged, it affects not only the neuron itself but also lesions elsewhere in its dominant site. After the CXCL1/CXCR2 axis is activated, multiple downstream pathways can be activated, such as c-Raf/MAPK/AP-1, p-PKC-μ/p-ILK/NLRP3, JAK2/STAT3, TAK1/NF-κB, etc. These pathways in turn mediate cellular motility state or cell migration. CXCR2 is expressed on the surface of neutrophils and monocytes/macrophages. These cells can be recruited to the lesion through the CXCL1/CXCR2 axis to participate in the inflammatory response. The expression of CXCR2 in neurons can activate some pathways in neurons through the CXCL1/CXCR2 axis, thereby causing damage to neurons. CXCR2 is also expressed in astrocytes, and when CXCR2 activated, it increases the number of astrocytes but impairs their function. Since inflammation can occur at almost any site of injury, elucidating the mechanism of CXCL1/CXCR2 axis' influence on inflammation may provide a favorable target for clinical treatment. Therefore, this article reviews the research progress of the CXCL1/CXCR2 axis in neurological diseases, aiming to provide a more meaningful theoretical basis for the treatment of neurological diseases.
C-X-C 趋化因子配体 (CXCL) 1 和其受体 C-X-C 趋化因子受体 (CXCR) 2 在周围神经系统 (PNS) 和中枢神经系统 (CNS) 中广泛表达,参与多种神经损伤后的炎症和疼痛发展。一旦神经受损,不仅影响神经元本身,还会影响其主导部位的其他病变。CXCL1/CXCR2 轴被激活后,可激活多个下游通路,如 c-Raf/MAPK/AP-1、p-PKC-μ/p-ILK/NLRP3、JAK2/STAT3、TAK1/NF-κB 等。这些通路反过来介导细胞迁移状态或细胞迁移。CXCR2 表达于中性粒细胞和单核细胞/巨噬细胞表面。这些细胞可以通过 CXCL1/CXCR2 轴募集到病变部位,参与炎症反应。神经元中的 CXCR2 通过 CXCL1/CXCR2 轴激活某些神经元通路,从而导致神经元损伤。CXCR2 也表达在星形胶质细胞中,当 CXCR2 被激活时,它会增加星形胶质细胞的数量,但会损害其功能。由于炎症几乎可以发生在损伤的任何部位,阐明 CXCL1/CXCR2 轴对炎症的影响机制可能为临床治疗提供有利的靶点。因此,本文综述了 CXCL1/CXCR2 轴在神经疾病中的研究进展,旨在为神经疾病的治疗提供更有意义的理论基础。