A leukotriene-dependent spleen-liver axis drives TNF production in systemic inflammation
| Autor: | Evilin Naname Komegae, Alexandre A. Steiner, Thayna S. Vieira, Monique T. Fonseca, Norberto Peporine Lopes, Lucas Miranda Marques, E. Moretti, William T. Festuccia, Camila F. Brito, Bianca F. Machado, Jady T. Guedes |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
MACRÓFAGOS Lipopolysaccharide Leukotriene B4 Spleen Systemic inflammation Biochemistry Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Molecular Biology 030304 developmental biology Inflammation 0303 health sciences Leukotriene Tumor Necrosis Factor-alpha Leukotriene B4 receptor Cell Biology Rats medicine.anatomical_structure Liver chemistry 030220 oncology & carcinogenesis Immunology lipids (amino acids peptides and proteins) Tumor necrosis factor alpha medicine.symptom |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1937-9145 1945-0877 |
| DOI: | 10.1126/scisignal.abb0969 |
| Popis: | Production of the proinflammatory cytokine tumor necrosis factor (TNF) must be precisely regulated for effective host immunity without the induction of collateral tissue damage. Here, we showed that TNF production was driven by a spleen-liver axis in a rat model of systemic inflammation induced by bacterial lipopolysaccharide (LPS). Analysis of cytokine expression and secretion in combination with splenectomy and hepatectomy revealed that the spleen generated not only TNF but also factors that enhanced TNF production by the liver, the latter of which accounted for nearly half of the TNF secreted into the circulation. Using mass spectrometry-based lipidomics, we identified leukotriene B4 (LTB4) as a candidate blood-borne messenger in this spleen-liver axis. LTB4 was essential for spleen-liver communication in vivo, as well as for humoral signaling between splenic macrophages and Kupffer cells in vitro. LPS stimulated the splenic macrophages to secrete LTB4, which primed Kupffer cells to secrete more TNF in response to LPS in a manner dependent on LTB4 receptors. These findings provide a framework to understand how systemic inflammation can be regulated at the level of interorgan communication. |
| Databáze: | OpenAIRE |
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