Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany; Institute of Experimental Pathology, Center for Molecular Biology of Inflammation, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany; Brandenburg Medical School (MHB), Fehrbelliner Str. 38, D-16816 Neuruppin, Germany.
Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Muenster, Von-Esmarch-Str. 56, D-48149 Muenster, Germany; Cluster of Excellence "Cells in Motion", University of Muenster, D-48149 Muenster, Germany.
Biochim Biophys Acta Mol Cell Res. 2019 Feb;1866(2):305-316. doi: 10.1016/j.bbamcr.2018.11.015. Epub 2018 Dec 4.
The innate immune system is the first line of defense against pathogenic threats. For the early pathogen recognition and activation of cell protective mechanisms, germline-encoded pattern recognition receptors (PRRs) detect characteristic and evolutionary conserved pathogen-associated molecular patterns (PAMPs). PRRs are therefore key elements in the innate immune response; in addition, they sense danger-associated molecular patterns (DAMPs) that are released by host cell molecules under pathophysiological conditions. Formyl peptide receptors (FPRs) are G-protein-coupled PRRs that respond to a surprisingly broad range of ligands, derived from both pathogens and host cells. Here, we exemplary discuss ligands in order to illustrate the wide pathophysiological relevance of the FPR signaling axis in case of e.g., chronic inflammations and to underscore its potential therapeutic value in the light of "biased agonism", a modern concept of GPCR (G-protein coupled receptors) activation. These novel insights into the GPCR receptor biochemistry will hopefully (re)stimulate FPR-related research and lead to novel strategies for the urgently needed development of drugs with pharmacologically advantageous characteristics.
先天免疫系统是抵御致病威胁的第一道防线。为了早期识别病原体并激活细胞保护机制，种系编码的模式识别受体（PRRs）可以识别特征性和进化保守的病原体相关分子模式（PAMPs）。因此，PRRs 是先天免疫反应的关键要素；此外，它们还可以感知在病理生理条件下由宿主细胞分子释放的危险相关分子模式（DAMPs）。甲酰肽受体（FPRs）是 G 蛋白偶联的 PRRs，可对来自病原体和宿主细胞的各种配体产生反应。在这里，我们举例讨论配体，以说明 FPR 信号轴在例如慢性炎症等情况下的广泛病理生理学相关性，并根据“偏向激动剂”这一现代 G 蛋白偶联受体（GPCR）激活概念强调其潜在的治疗价值。这些对 GPCR 受体生物化学的新见解有望（重新）激发与 FPR 相关的研究，并为急需开发具有药理优势特征的药物提供新策略。
