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Annals of Intensive Care
Published in: Annals of Intensive Care 1/2016

Open Access 01-12-2016 | Research

Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity

Authors: Marie-Alix Espinasse, David Hajage, Philippe Montravers, Pascale Piednoir, Guillaume Dufour, Florence Tubach, Vanessa Granger, Luc de Chaisemartin, Benoît Noël, Marc Pallardy, Sylvie Chollet-Martin, Armelle Biola-Vidamment

Published in: Annals of Intensive Care | Issue 1/2016

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Abstract

Background

Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein involved in neutrophil apoptosis and the resolution of inflammation. Given the numerous pathophysiologic roles of neutrophils in the acute respiratory distress syndrome (ARDS), we postulated that neutrophil GILZ expression might be induced during ARDS, to modulate the inflammatory process and participate in lung repair.

Methods

This single-center, prospective, observational cohort study took place in the surgical intensive care unit of Bichat Hospital (Paris, France) and involved 17 ARDS patients meeting the Berlin criteria at inclusion, and 14 ventilated controls without ARDS. Serial blood samples were obtained every 2 days until extubation or death (from 1 to 9 samples per patient). GILZ protein and gene expression was quantified in blood neutrophils, along with markers of inflammation (CRP, extracellular DNA) or its resolution (Annexin A1).

Results

Neutrophil GILZ expression was detected at the transcriptional and/or translational level in 9/17 ARDS patients (in particular 7/10 severe ARDS) and in 2/14 ventilated controls. The highest mRNA levels were observed in the most severely ill patients (p < 0.028). GILZ was expressed in about ¾ of the corticosteroid-treated patients and its expression could also occur independently of corticosteroids, suggesting that inflammatory signals may also induce neutrophil GILZ expression in vivo.

Conclusions

In this pilot study, we show for the first time that blood neutrophils from patients with ARDS can express GILZ, in keeping with an anti-inflammatory and regulatory endogenous role of GILZ in humans. Contrary to some markers of inflammation or its resolution, the levels of gilz gene expression were related to ARDS severity.
Literature
1.
Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–33.PubMed
2.
Williams AE, Chambers RC. The mercurial nature of neutrophils: Still an enigma in ARDS? Am J Physiol Lung Cell Mol Physiol. 2014;306(3):L217–30.CrossRefPubMed
3.
Fialkow L, Fochesatto Filho L, Bozzetti MC, Milani AR, Rodrigues Filho EM, Ladniuk RM, et al. Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome. Crit Care. 2006;10(6):R155.CrossRefPubMedPubMedCentral
4.
Chopra M, Reuben JS, Sharma AC. Acute lung injury: apoptosis and signaling mechanisms. Exp Biol Med (Maywood). 2009;234(4):361–71.CrossRef
5.
Klinzing S, Wenger U, Steiger P, Starck CT, Wilhelm M, Schuepbach RA, et al. External validation of scores proposed for estimation of survival probability of patients with severe adult respiratory distress syndrome undergoing extracorporeal membrane oxygenation therapy: a retrospective study. Crit Care. 2015;19:142.CrossRefPubMedPubMedCentral
6.
Monsel A, Zhu YG, Gennai S, Hao Q, Hu S, Rouby JJ, et al. Therapeutic effects of human mesenchymal stem cell-derived microvesicles in severe pneumonia in mice. Am J Respir Crit Care Med. 2015;192(3):324–36.CrossRefPubMedPubMedCentral
7.
Cardinal-Fernandez P, Ferruelo A, Esteban A, Lorente JA. Characteristics of micro RNAs and their potential relevance for the diagnosis and therapy of the acute respiratory distress syndrome: from bench to bedside. Transl Res. 2016;169:102–11.CrossRefPubMed
8.
Yu ZX, Ji MS, Yan J, Cai Y, Liu J, Yang HF, et al. The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome. Crit Care. 2015;19:82.CrossRefPubMedPubMedCentral
9.
Horita N, Hashimoto S, Miyazawa N, Fujita H, Kojima R, Inoue M, et al. Impact of corticosteroids on mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis. Intern Med. 2015;54(12):1473–9.CrossRefPubMed
10.
Meduri GU, Bridges L, Shih MC, Marik PE, Siemieniuk RA, Kocak M. Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients’ data from four randomized trials and trial-level meta-analysis of the updated literature. Intensive Care Med. 2016;42:829–40.CrossRefPubMed
11.
Ayroldi E, Riccardi C. Glucocorticoid-induced leucine zipper (GILZ): a new important mediator of glucocorticoid action. Faseb J. 2009;23(11):3649–58.CrossRefPubMed
12.
Beaulieu E, Morand EF. Role of GILZ in immune regulation, glucocorticoid actions and rheumatoid arthritis. Nat Rev. 2011;7(6):340–8.
13.
Beaulieu E, Ngo D, Santos L, Yang YH, Smith M, Jorgensen C, et al. Glucocorticoid-induced leucine zipper is an endogenous antiinflammatory mediator in arthritis. Arthritis Rheum. 2010;62(9):2651–61.CrossRefPubMed
14.
Latre de Late P, Pepin A, Assaf-Vandecasteele H, Espinasse C, Nicolas V, Asselin-Labat ML, et al. Glucocorticoid-induced leucine zipper (GILZ) promotes the nuclear exclusion of FOXO3 in a Crm1-dependent manner. J Biol Chem. 2010;285(8):5594–605.CrossRefPubMed
15.
Asselin-Labat ML, David M, Biola-Vidamment A, Lecoeuche D, Zennaro MC, Bertoglio J, et al. GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis. Blood. 2004;104(1):215–23.CrossRefPubMed
16.
Pepin A, Espinasse MA, Latre de Late P, Szely N, Pallardy M, Biola-Vidamment A. TSC-22 promotes interleukin-2-deprivation induced apoptosis in T-lymphocytes. J Cell Biochem. 2016;117(8):1855–68.CrossRefPubMed
17.
Espinasse MA, Pepin A, Virault-Rocroy P, Szely N, Chollet-Martin S, Pallardy M, et al. Glucocorticoid-induced leucine zipper is expressed in human neutrophils and promotes apoptosis through Mcl-1 down-regulation. J Innate Immun. 2016;8(1):81–96.CrossRefPubMed
18.
Vago JP, Tavares LP, Garcia CC, Lima KM, Perucci LO, Vieira EL, et al. The role and effects of glucocorticoid-induced leucine zipper in the context of inflammation resolution. J Immunol. 2015;194(10):4940–50.CrossRefPubMed
19.
Yang YH, Aeberli D, Dacumos A, Xue JR, Morand EF. Annexin-1 regulates macrophage IL-6 and TNF via glucocorticoid-induced leucine zipper. J Immunol. 2009;183(2):1435–45.CrossRefPubMed
20.
Vago JP, Nogueira CR, Tavares LP, Soriani FM, Lopes F, Russo RC, et al. Annexin A1 modulates natural and glucocorticoid-induced resolution of inflammation by enhancing neutrophil apoptosis. J Leukoc Biol. 2012;92(2):249–58.CrossRefPubMed
21.
Le Gall JR, Lemeshow S, Saulnier F. A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270(24):2957–63.CrossRefPubMed
22.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10.CrossRefPubMed
23.
Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988;138(3):720–3.CrossRefPubMed
24.
Bein T, Grasso S, Moerer O, Quintel M, Guerin C, Deja M, et al. The standard of care of patients with ARDS: ventilatory settings and rescue therapies for refractory hypoxemia. Intensive Care Med. 2016;42(5):699–711.CrossRefPubMedPubMedCentral
25.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.CrossRefPubMed
26.
Barrientos L, Marin-Esteban V, de Chaisemartin L, Le-Moal VL, Sandre C, Bianchini E, et al. An improved strategy to recover large fragments of functional human neutrophil extracellular traps. Front Immunol. 2013;4:166.CrossRefPubMedPubMedCentral
27.
Barrientos L, Bignon A, Gueguen C, de Chaisemartin L, Gorges R, Sandre C, et al. Neutrophil extracellular traps downregulate lipopolysaccharide-induced activation of monocyte-derived dendritic cells. J Immunol. 2014;193(11):5689–98.CrossRefPubMed
28.
Migdal C, Botton J, El Ali Z, Azoury ME, Guldemann J, Gimenez-Arnau E, et al. Reactivity of chemical sensitizers toward amino acids in cellulo plays a role in the activation of the Nrf2-ARE pathway in human monocyte dendritic cells and the THP-1 cell line. Toxicol Sci. 2013;133(2):259–74.CrossRefPubMed
29.
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002;3(7):RESEARCH0034.CrossRefPubMedPubMedCentral
30.
31.
Hellemans J, Mortier G, De Paepe A, Speleman F, Vandesompele J. qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data. Genome Biol. 2007;8(2):R19.CrossRefPubMedPubMedCentral
32.
Allou N, Bronchard R, Guglielminotti J, Dilly MP, Provenchere S, Lucet JC, et al. Risk factors for postoperative pneumonia after cardiac surgery and development of a preoperative risk score. Crit Care Med. 2014;42(5):1150–6.CrossRefPubMed
33.
Summers C, Singh NR, White JF, Mackenzie IM, Johnston A, Solanki C, et al. Pulmonary retention of primed neutrophils: a novel protective host response, which is impaired in the acute respiratory distress syndrome. Thorax. 2014;69(7):623–9.CrossRefPubMedPubMedCentral
34.
35.
Scapini P, Cassatella MA. Social networking of human neutrophils within the immune system. Blood. 2014;124(5):710–9.CrossRefPubMed
36.
Kangelaris KN, Prakash A, Liu KD, Aouizerat B, Woodruff PG, Erle DJ, et al. Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS. Am J Physiol Lung Cell Mol Physiol. 2015;308(11):L1102–13.CrossRefPubMedPubMedCentral
37.
Hoppstadter J, Diesel B, Eifler LK, Schmid T, Brune B, Kiemer AK. Glucocorticoid-induced leucine zipper is downregulated in human alveolar macrophages upon Toll-like receptor activation. Eur J Immunol. 2012;42(5):1282–93.CrossRefPubMed
38.
Sharma NS, Wille KM, Zhi D, Thannickal VJ, Brodie DM, Hoopes CW, et al. Use of ECMO in the management of severe acute respiratory distress syndrome: a survey of academic medical centers in the United States. ASAIO J. 2015;61(5):556–63.CrossRefPubMed
39.
Maclaren G, Butt W. Extracorporeal membrane oxygenation and sepsis. Crit Care Resusc. 2007;9(1):76–80.PubMed
40.
Chen Q, Yu W, Shi J, Shen J, Hu Y, Gong J, et al. The effect of extracorporeal membrane oxygenation therapy on systemic oxidative stress injury in a porcine model. Artif Organs. 2014;38(5):426–31.CrossRefPubMed
41.
42.
Yildiz C, Palaniyar N, Otulakowski G, Khan MA, Post M, Kuebler WM, et al. Mechanical ventilation induces neutrophil extracellular trap formation. Anesthesiology. 2015;122(4):864–75.CrossRefPubMed
43.
Zhang Y, Wen Z, Guan L, Jiang P, Gu T, Zhao J, et al. Extracellular histones play an inflammatory role in acid aspiration-induced acute respiratory distress syndrome. Anesthesiology. 2015;122(1):127–39.CrossRefPubMed
44.
Caudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, Monestier M, et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Investig. 2012;122(7):2661–71.CrossRefPubMedPubMedCentral
45.
Wang Y, Ma YY, Song XL, Cai HY, Chen JC, Song LN, et al. Upregulations of glucocorticoid-induced leucine zipper by hypoxia and glucocorticoid inhibit proinflammatory cytokines under hypoxic conditions in macrophages. J Immunol. 2012;188(1):222–9.CrossRefPubMed
46.
Lim W, Park C, Shim MK, Lee YH, Lee YM, Lee Y. Glucocorticoids suppress hypoxia-induced COX-2 and hypoxia inducible factor-1alpha expression through the induction of glucocorticoid-induced leucine zipper. Br J Pharmacol. 2014;171(3):735–45.CrossRefPubMedPubMedCentral
47.
Marwick JA, Dorward DA, Lucas CD, Jones KO, Sheldrake TA, Fox S, et al. Oxygen levels determine the ability of glucocorticoids to influence neutrophil survival in inflammatory environments. J Leukoc Biol. 2013;94(6):1285–92.CrossRefPubMedPubMedCentral
48.
49.
Sugimoto MA, Vago JP, Teixeira MM, Sousa LP. Annexin A1 and the resolution of inflammation: modulation of neutrophil recruitment, apoptosis, and clearance. J Immunol Res. 2016;2016:8239258.CrossRefPubMedPubMedCentral
50.
Peters SA, Bots ML, den Ruijter HM, Palmer MK, Grobbee DE, Crouse JR 3rd, et al. Multiple imputation of missing repeated outcome measurements did not add to linear mixed-effects models. J Clin Epidemiol. 2012;65(6):686–95.CrossRefPubMed
51.
Kurland BF, Johnson LL, Egleston BL, Diehr PH. Longitudinal data with follow-up truncated by death: match the analysis method to research aims. Stat Sci. 2009;24(2):211.CrossRefPubMedPubMedCentral
Metadata
Title
Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity
Authors
Marie-Alix Espinasse
David Hajage
Philippe Montravers
Pascale Piednoir
Guillaume Dufour
Florence Tubach
Vanessa Granger
Luc de Chaisemartin
Benoît Noël
Marc Pallardy
Sylvie Chollet-Martin
Armelle Biola-Vidamment
Publication date
01-12-2016
Publisher
Springer Paris
Published in
Annals of Intensive Care / Issue 1/2016
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-016-0210-0

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