Autor: |
Ashti M. Shah, Ruben Zamora, Derek Barclay, Jinling Yin, Fayten El-Dehaibi, Meghan Addorisio, Tea Tsaava, Aisling Tynan, Kevin Tracey, Sangeeta S. Chavan, Yoram Vodovotz |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
|
Zdroj: |
Frontiers in Systems Biology, Vol 4 (2024) |
Druh dokumentu: |
article |
ISSN: |
2674-0702 |
DOI: |
10.3389/fsysb.2024.1266279 |
Popis: |
Introduction: The vagus nerve innervates multiple organs, but its role in regulating cross-tissue spread of inflammation is as yet unclear. We hypothesized that the vagus nerve may regulate cross-tissue inflammation via modulation of the putatively neurally regulated chemokine IP-10/CXCL10.Methods: Rate-of-change analysis, dynamic network analysis, and dynamic hypergraphs were used to model intra- and inter-tissue trends, respectively, in inflammatory mediators from mice that underwent either vagotomy or sham surgery.Results: This analysis suggested that vagotomy primarily disrupts the cross-tissue attenuation of inflammatory networks involving IP-10 as well as the chemokines MIG/CXCL9 and CCL2/MCP-1 along with the cytokines IFN-γ and IL-6. Computational analysis also suggested that the vagus-dependent rate of expression of IP-10 and MIG/CXCL9 in the spleen impacts the trajectory of chemokine expression in other tissues. Perturbation of this complex system with bacterial lipopolysaccharide (LPS) revealed a vagally regulated role for MIG in the heart. Further, LPS-stimulated expression of IP-10 was inferred to be vagus-independent across all tissues examined while reducing connectivity to IL-6 and MCP-1, a hypothesis supported by Boolean network modeling.Discussion: Together, these studies define novel spatiotemporal dimensions of vagus-regulated acute inflammation. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|