| Full text | |
| Author(s): Show less - |
Fonseca, Monique T.
;
Moretti, Eduardo H.
;
Marques, Lucas M. M.
;
Machado, Bianca F.
;
Brito, Camila F.
;
Guedes, Jady T.
;
Komegae, Evilin N.
;
Vieira, Thayna S.
;
Festuccia, William T.
;
Lopes, Norberto P.
;
Steiner, Alexandre A.
Total Authors: 11
|
| Document type: | Journal article |
| Source: | SCIENCE SIGNALING; v. 14, n. 679, p. 12-pg., 2021-04-20. |
| Abstract | |
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 B-4 (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. (AU) | |
| FAPESP's process: | 18/00849-0 - Hemodynamic evaluation in non-anesthetized rats |
| Grantee: | Jady Tamaio Guedes da Silva |
| Support Opportunities: | Scholarships in Brazil - Technical Training Program - Technical Training |
| FAPESP's process: | 16/23540-9 - Role of cyclooxygenase-1 in the generation of inflammatory mediators |
| Grantee: | Bianca de Freitas Machado |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 17/13350-0 - The temperature negatively regulates the microbicidal activity of macrophages: why do they kill more in hypothermia? |
| Grantee: | Monique Thaís Costa Fonseca |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 16/04921-1 - Arterial tonus in septic shock: a new facet to an old problem. |
| Grantee: | Alexandre Alarcon Steiner |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/03418-0 - Hypothermia in Sepsis: causes and consequences |
| Grantee: | Alexandre Alarcon Steiner |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases |
| Grantee: | William Tadeu Lara Festuccia |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 14/03719-9 - Role of leptin in regulation of systemic inflammation |
| Grantee: | Evilin Naname Komegae |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/09399-7 - Development of hypothermia in systemic inflammation: the brain hypoxia hypothesis |
| Grantee: | Eduardo Hermogenes Moretti |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 17/17403-1 - Characterization of the molecular mechanisms by which TSC1 deletion in adipocytes increases oxidative metabolism and UCP1 content in white adipose tissue |
| Grantee: | Thayna dos Santos Vieira |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation |
| Grantee: | Norberto Peporine Lopes |
| Support Opportunities: | BIOTA-FAPESP Program - Thematic Grants |