1. Critical Neurotransmitters in the Neuroimmune Network
Thomas Wesley Hodo, Maria Teresa Prudente de Aquino, Akiko Shimamoto, Anil Shanker Front Immunol. 2020 Aug 21;11:1869. doi: 10.3389/fimmu.2020.01869. eCollection 2020.
Immune cells rely on cell-cell communication to specify and fine-tune their responses. They express an extensive network of cell communication modes, including a vast repertoire of cell surface and transmembrane receptors and ligands, membrane vesicles, junctions, ligand and voltage-gated ion channels, and transporters. During a crosstalk between the nervous system and the immune system these modes of cellular communication and the downstream signal transduction events are influenced by neurotransmitters present in the local tissue environments in an autocrine or paracrine fashion. Neurotransmitters thus influence innate and adaptive immune responses. In addition, immune cells send signals to the brain through cytokines, and are present in the brain to influence neural responses. Altered communication between the nervous and immune systems is emerging as a common feature in neurodegenerative and immunopathological diseases. Here, we present the mechanistic frameworks of immunostimulatory and immunosuppressive effects critical neurotransmitters - dopamine (3,4-dihydroxyphenethylamine), serotonin (5-hydroxytryptamine), substance P (trifluoroacetate salt powder), and L-glutamate - exert on lymphocytes and non-lymphoid immune cells. Furthermore, we discuss the possible roles neurotransmitter-driven neuroimmune networks play in the pathogenesis of neurodegenerative disorders, autoimmune diseases, cancer, and outline potential clinical implications of balancing neuroimmune crosstalk by therapeutic modulation.
2. (R)-1-Phenyl-ethyl-ammonium trifluoro-acetate
María-Guadalupe Hernández Linares, Gabriel Guerrero Luna, Sylvain Bernès Acta Crystallogr Sect E Struct Rep Online. 2010 Apr 21;66(Pt 5):o1118. doi: 10.1107/S1600536810013565.
In the crystal structure of the title salt, C(8)H(12)N(+)·C(2)F(3)O(2) (-), all of the ammonium H atoms serve as donors for hydrogen bonds to carboxyl-ate O atoms, forming an R(4) (3)(10) ring motif based on two cations and two anions. Since both cations and anions act as inter-ion bridging groups, R(10) rings aggregate in a one-dimensional supra-molecular network by sharing the strongest N-H⋯O bond. Edge-sharing motifs lie on the twofold screw axis parallel to [010], and anti-parallel packing of these 2(1)-column structural units results in the crystal structure. This arrangement is one of the most commonly occurring in conglomerates of chiral 1-phenyl-ethyl-amine with achiral monocarboxylic acids, confirming that these ionic salts are particularly robust supra-molecular heterosynthons useful in crystal engineering.
3. PAR2 promotes M1 macrophage polarization and inflammation via FOXO1 pathway
Liang Chen, Beiyao Gao, Yadong Zhang, Hanyu Lu, Xiaobo Li, Luanfeng Pan, Lianhua Yin, Xiuling Zhi J Cell Biochem. 2019 Jun;120(6):9799-9809. doi: 10.1002/jcb.28260. Epub 2018 Dec 14.
Macrophages polarization plays essential but different roles in most diseases such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Our previous study revealed that protease-activated receptor 2 (PAR2), a G-protein coupled receptor influenced macrophage function, but little is known regarding the regulation of macrophage polarization process and its potential mechanisms. In the present study, bone marrow-derived macrophages (BMDM) isolated from C57/BL6 mice and cultured with L929-conditional medium and murine macrophage cell line RAW264.7 were used to study the function of PAR2 activation in vitro. BMDM was stimulated by the small molecular PAR2 agonist, 2-furoyl-LIGRLO-amide trifluoroacetate salt, followed by transcription factor microarray to screen the significantly activated signaling pathways under PAR2 activation. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the expression of targeted genes and transcription factors. Immunofluorescence was used to observe the subcellular distribution of transcription factors. Our results demonstrated that M1-like polarization was presented by PAR2 agonist treatment with significant upregulation of interleukin-1β, interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-α in BMDM and RAW264.7. Microarray identified forkhead box protein O1 (FOXO1) was significantly increased under PAR2 agonist stimulation, which was confirmed by qPCR and Western blot analysis. Immunofluorescence demonstrated that increased FOXO1 accumulated in the nucleus, which is necessary to promote transcription for targeted genes. We further knocked down FOXO1 expression using small interfering RNA, which alleviated PAR2-induced proinflammatory gene expression. The PAR2/FOXO1 pathway mediated stimulation of proinflammatory genes was further confirmed by tryptase, an endogenous ligand of PAR2. In conclusion, this study demonstrated that PAR2 activation-induced M1 polarization and inflammation through the FOXO1-dependent pathway.
