Overexpression of GILZ in macrophages limits systemic inflammation while increasing bacterial clearance in sepsis in mice.
Mehdi EllouzeLola VigourouxColas TcherakianPaul-Louis WoertherAurélie GuguinOlivier RobertMathieu SurenaudThi TranJoseph CalmetteThomas BarbinGabriel PerlemuterAnne-Marie CassardPierre LaunayVirginie MaximeDjillali AnnaneYves LevyVéronique GodotPublished in: European journal of immunology (2020)
Studies support the beneficial effects of glucocorticoids (GCs) during septic shock, steering research toward the potential role of GC-induced proteins in controlling excessive inflammatory responses. GILZ is a glucocorticoid-induced protein involved in the anti-inflammatory effects of GCs. We investigated whether the overexpression of GILZ specifically limited to monocytes and macrophages (M/M) alone could control inflammation, thus improving the outcome of septic shock in animal models. We also monitored the expression of GILZ in M/M from septic mice and septic-shock patients. M/M from patients and septic mice displayed significantly lower expression of GILZ than those isolated from controls. Furthermore, transgenic mice (Tg-mice) experiencing sepsis, with increased expression of GILZ restricted to M/M, showed lower frequencies of inflammatory monocytes than their littermates and lower plasma levels of inflammatory cytokines. Tg-mice also had lower blood bacterial counts. We further established that the upregulation of GILZ in M/M enhanced their phagocytic capacity in in vivo assays. The increase of GILZ in M/M was also sufficient to improve the survival rates of septic mice. These results provide evidence for a central role of both GILZ and M/M in the pathophysiology of septic shock and a possible clue for the modulation of inflammation in this disease.
Keyphrases
- septic shock
- high fat diet induced
- poor prognosis
- oxidative stress
- acute kidney injury
- end stage renal disease
- newly diagnosed
- ejection fraction
- cell proliferation
- prognostic factors
- anti inflammatory
- diabetic rats
- high glucose
- wild type
- high throughput
- type diabetes
- peripheral blood
- long non coding rna
- climate change
- insulin resistance
- adipose tissue
- risk assessment
- physical activity
- mass spectrometry
- single cell