Dermitzaki Eirini, Venihaki Maria, Tsatsanis Christos, Gravanis Achille, Avgoustinaki Pavlina D, Liapakis George, Margioris Andrew N
Department of Clinical Chemistry, School of Medicine, University of Crete, Crete. Greece.
Department of Pharmacology, School of Medicine, University of Crete, Crete. Greece.
Curr Mol Pharmacol. 2018;11(1):39-50. doi: 10.2174/1874467210666170109164430.
The corticotropin releasing factor (CRF) family of neuropeptides, CRF and the Urocortins, and their receptors are present not only within the central nervous system but also in the periphery at various locations and at the sites of inflammation where they influence its progress in a complex local / paracrine manner.
This review summarizes current knowledge regarding the regulation of inflammatory process by CRF family of neuropeptides and receptors with a special sight into their role in inflammatory pain and in chronic low grade inflammation that occurs in obesity. For this purpose, we searched for relevant peer-reviewed research articles using bibliographic databases.
The CRF neuropeptides are either produced locally, by components of the inflammatory response or they may reach the inflammation sites via postganglionic sympathetic and sensory afferent nerve transport. It now appears that most immune cells taking part in the inflammatory process express CRF receptor type 1 (CRF1R) and type 2 (CRF2R) and thus represent targets of CRF neuropeptides. Indeed, mast cells, monocytes / macrophages, neutrophils and other types of immune cells express both types of the CRF receptors. In addition to their role in the pathophysiology of inflammation, CRF and its receptors also exert modulatory effects on inflammatory pain. Finally, it now appears that the CRF system is also present in adipose tissue and may play a crucial role in the development of the chronic low grade inflammation, which is characteristic of obesity.
The local effects of the CRF family of neuropeptides can be either pro- or antiinflammatory depending on concentration of each type of neuropeptide present and the ratio of the local expression of their receptors CRF1R and CRF2R.
促肾上腺皮质激素释放因子(CRF)神经肽家族,包括CRF和尿皮质素,及其受体不仅存在于中枢神经系统,还存在于外周的各个部位以及炎症部位,它们以复杂的局部/旁分泌方式影响炎症进展。
本综述总结了关于CRF神经肽家族及其受体对炎症过程调节的现有知识,特别关注它们在炎性疼痛和肥胖中发生的慢性低度炎症中的作用。为此,我们使用文献数据库搜索了相关的同行评审研究文章。
CRF神经肽要么由炎症反应的成分在局部产生,要么可能通过节后交感神经和感觉传入神经运输到达炎症部位。现在看来,大多数参与炎症过程的免疫细胞都表达1型CRF受体(CRF1R)和2型CRF受体(CRF2R),因此是CRF神经肽的作用靶点。事实上,肥大细胞、单核细胞/巨噬细胞、中性粒细胞和其他类型的免疫细胞都表达这两种类型的CRF受体。除了在炎症病理生理学中的作用外,CRF及其受体对炎性疼痛也有调节作用。最后,现在看来CRF系统也存在于脂肪组织中,可能在肥胖特有的慢性低度炎症的发展中起关键作用。
CRF神经肽家族的局部作用可能是促炎或抗炎的,这取决于每种神经肽的浓度以及它们的受体CRF1R和CRF2R的局部表达比例。