Overexpression of GILZ in macrophages limits systemic inflammation while increasing bacterial clearance in sepsis in mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Immunology Année : 2020

Overexpression of GILZ in macrophages limits systemic inflammation while increasing bacterial clearance in sepsis in mice

Colas Tcherakian
  • Fonction : Auteur
Paul‐louis Woerther
Olivier Robert
Thi Tran
  • Fonction : Auteur
Joseph Calmette
  • Fonction : Auteur
Gabriel Perlemuter
Anne‐marie Cassard
  • Fonction : Auteur
Pierre Launay

Résumé

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. Keywords: GILZ; inflammation; monocytes/macrophages; phagocytosis; sepsis. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dates et versions

hal-03623484 , version 1 (29-03-2022)

Identifiants

Citer

Mehdi Ellouze, Lola Vigouroux, Colas Tcherakian, Paul‐louis Woerther, Aurélie Guguin, et al.. Overexpression of GILZ in macrophages limits systemic inflammation while increasing bacterial clearance in sepsis in mice. European Journal of Immunology, 2020, 50 (4), pp.589-602. ⟨10.1002/eji.201948278⟩. ⟨hal-03623484⟩
38 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More