IL-33 Attenuates Sepsis by Inhibiting IL-17 Receptor Signaling through Upregulation of SOCS3.
Cell Physiol Biochem
; 42(5): 1961-1972, 2017.
Article
in En
| MEDLINE
| ID: mdl-28793286
ABSTRACT
BACKGROUND/AIMS:
Sepsis is a systemic inflammatory response during infection. There are limited therapeutic options for sepsis patients. Interleukin (IL)-33 has been reported recently with a beneficial effect in mouse sepsis.METHODS:
In this study, we initiated a clinical study to measure serum levels of pro-inflammatory cytokines including IL-33 in sepsis patients. Next, we employed cecal ligation and puncture (CLP) to study the role of IL-33 during sepsis. To further dissect the molecular mechanism, we used in vivo knockout models and in vitro knockdown murine embryonic fibroblasts (MEFs) to investigate the cross-talk between IL-33 and IL-17 signaling, and to identify the potential downstream mediators.RESULTS:
IL-33 and IL-17 were upregulated in both clinical and experimental sepsis. In CLP, IL-33 (-/-) mice showed higher mortality rate, and IL-33 treatment improved the survival rate. Elevated proinflammatory cytokines in sepsis were related to IL-17 from γδT cells. IL-33 treatment suppressed production of these cytokines by targeting IL-17 signaling both in vivo and in vitro. Finally, IL-33 was shown to inhibit the IL-17 pathway via activating suppressor of cytokine signaling (SOCS)-3.CONCLUSION:
Collectively, the results suggest that IL-33 plays a negative regulatory role in sepsis progression by inhibiting IL-17 pathway through activating SOCS3. This finding would inspire a new therapeutic strategy for treating sepsis.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Systemic Inflammatory Response Syndrome
/
Sepsis
/
Receptors, Interleukin-17
/
Interleukin-33
/
Suppressor of Cytokine Signaling 3 Protein
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell Physiol Biochem
Journal subject:
BIOQUIMICA
/
FARMACOLOGIA
Year:
2017
Document type:
Article
Publication country:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY