Sympathetic nervous system controls resolution of inflammation via regulation of repulsive guidance molecule A
Autor: | Georg Hansmann, Andreas Körner, Martin Schlegel, Verena Gudernatsch, Timo Schumacher, Martin Giera, Torsten Kaussen, Valbona Mirakaj |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Agonist Nervous system Sympathetic nervous system Sympathetic Nervous System Neutrophils medicine.drug_class Science General Physics and Astronomy Nerve Tissue Proteins Inflammation 02 engineering and technology Peritonitis GPI-Linked Proteins Article General Biochemistry Genetics and Molecular Biology Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences Immune system medicine Animals Humans lcsh:Science PI3K/AKT/mTOR pathway Multidisciplinary Chemistry Macrophages Monocyte NF-kappa B General Chemistry Repulsive guidance molecule A 021001 nanoscience & nanotechnology Cell biology 030104 developmental biology medicine.anatomical_structure Female lcsh:Q medicine.symptom 0210 nano-technology Proto-Oncogene Proteins c-akt |
Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications, 10 Nature Communications |
ISSN: | 2041-1723 |
Popis: | The bidirectional communication between the immune and nervous system is important in regulating immune responses. Here we show that the adrenergic nerves of sympathetic nervous system orchestrate inflammation resolution and regenerative programs by modulating repulsive guidance molecule A (RGM-A). In murine peritonitis, adrenergic nerves and RGM-A show bidirectional activation by stimulating the mutual expression and exhibit a higher potency for the cessation of neutrophil infiltration; this reduction is accompanied by increased pro-resolving monocyte or macrophage recruitment, polymorphonucleocyte clearance and specialized pro-resolving lipid mediators production at sites of injury. Chemical sympathectomy results in hyperinflammation and ineffective resolution in mice, while RGM-A treatments reverse these phenotypes. Signalling network analyses imply that RGM-A and β2AR agonist regulate monocyte activation by suppressing NF-κB activity but activating RICTOR and PI3K/AKT signalling. Our results thus illustrate the function of sympathetic nervous system and RGM-A in regulating resolution and tissue repair in a murine acute peritonitis model. Diverse interactions between the nervous and immune systems have been shown, but specific mechanistic insights are still lacking. Here the authors show, using both mouse inflammation models and clinical correlation, that adrenergic nerve may ameliorate inflammation by inducing repulsive guidance molecule A signalling. |
Databáze: | OpenAIRE |
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