Interleukin-3 Plays a Vital Role in Hyperoxic Acute Lung Injury in Mice Via Mediating Inflammation

Overview

Journal BMC Pulm Med

Publisher Biomed Central

Specialty Pulmonary Medicine

Date 2018 Oct 31

PMID 30373540

Citations 5

Authors

Zhijian Huang

Wei Zhang

Jian Yang

Feiyu Sun

Hongwei Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Interleukin (IL)-3 amplifies inflammation. However, the effect of IL-3 in acute lung injury (ALI), an acute inflammatory disease, is unclear. The aim of this study was to test the hypothesis that IL-3 plays an important role in hyperoxia-induced ALI.

Methods: Hyperoxic ALI was induced in wild-type (WT) and IL-3 gene disrupted (IL-3) mice by exposure to 100% O for 72 h.

Results: Hyperoxia increased IL-3 levels in plasma and lung tissues in WT mice. Pulmonary inflammation and edema were detected by histological assay in WT mice exposed to 100% O for 72 h. However, the hyperoxia-induced lung histological changes were improved in IL-3 mice. The hyperoxia-induced elevation of neutrophils in bronchoalveolar lavage fluids and circulation were reduced in IL-3 mice. Meanwhile, the levels of tumor necrosis factor-α and IL-6 were suppressed in IL-3 mice compared with WT mice. Moreover, the hyperoxia-induced the activation of IκBα kinase (IKK) β, IκBα phosphorylation, and nuclear factor-κB translocation were inhibited in IL-3 mice compared with WT mice.

Conclusions: Our results suggest IL-3 is a potential therapeutic target for hyperoxia-induced ALI.

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References

Singha A, Bhattacharjee B, Saha B, Maiti D . IL-3 and GM-CSF modulate functions of splenic macrophages in ENU induced leukemia. Cytokine. 2017; 91:89-95. DOI: 10.1016/j.cyto.2016.12.009. View

Tao W, Li P, Yang L, Ma Y . Effects of a Soluble Epoxide Hydrolase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury in Mice. PLoS One. 2016; 11(8):e0160359. PMC: 4973880. DOI: 10.1371/journal.pone.0160359. View

Borriello F, Iannone R, Di Somma S, Loffredo S, Scamardella E, Galdiero M . GM-CSF and IL-3 Modulate Human Monocyte TNF-α Production and Renewal in Models of Trained Immunity. Front Immunol. 2017; 7:680. PMC: 5237654. DOI: 10.3389/fimmu.2016.00680. View

Schroeder J, Chichester K, Bieneman A . Human basophils secrete IL-3: evidence of autocrine priming for phenotypic and functional responses in allergic disease. J Immunol. 2009; 182(4):2432-8. PMC: 2704022. DOI: 10.4049/jimmunol.0801782. View

Gotts J, Matthay M . Sepsis: pathophysiology and clinical management. BMJ. 2016; 353:i1585. DOI: 10.1136/bmj.i1585. View

Weber G, Chousterman B, He S, Fenn A, Nairz M, Anzai A . Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis. Science. 2015; 347(6227):1260-5. PMC: 4376966. DOI: 10.1126/science.aaa4268. View

Wheeler A, Bernard G . Acute lung injury and the acute respiratory distress syndrome: a clinical review. Lancet. 2007; 369(9572):1553-1564. DOI: 10.1016/S0140-6736(07)60604-7. View

Aschner Y, Zemans R, Yamashita C, Downey G . Matrix metalloproteinases and protein tyrosine kinases: potential novel targets in acute lung injury and ARDS. Chest. 2014; 146(4):1081-1091. PMC: 4188143. DOI: 10.1378/chest.14-0397. View

Tao W, Shu Y, Miao Q, Zhu Y . Attenuation of hyperoxia-induced lung injury in rats by adrenomedullin. Inflammation. 2011; 35(1):150-7. DOI: 10.1007/s10753-011-9300-1. View

10.

Matthay M, Idell S . Update on acute lung injury and critical care medicine 2009. Am J Respir Crit Care Med. 2010; 181(10):1027-32. PMC: 3269230. DOI: 10.1164/rccm.201001-0074UP. View

11.

Williams G, Smith C, Spooncer E, Dexter T, Taylor D . Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature. 1990; 343(6253):76-9. DOI: 10.1038/343076a0. View

12.

Hara T, Miyajima A . Function and signal transduction mediated by the interleukin 3 receptor system in hematopoiesis. Stem Cells. 1996; 14(6):605-18. DOI: 10.1002/stem.140605. View

13.

Masterson C, OToole D, Leo A, McHale P, Horie S, Devaney J . Effects and Mechanisms by Which Hypercapnic Acidosis Inhibits Sepsis-Induced Canonical Nuclear Factor-κB Signaling in the Lung. Crit Care Med. 2015; 44(4):e207-17. DOI: 10.1097/CCM.0000000000001376. View

14.

Meduri G, Annane D, Chrousos G, Marik P, Sinclair S . Activation and regulation of systemic inflammation in ARDS: rationale for prolonged glucocorticoid therapy. Chest. 2009; 136(6):1631-1643. DOI: 10.1378/chest.08-2408. View

15.

Hinz M, Scheidereit C . The IκB kinase complex in NF-κB regulation and beyond. EMBO Rep. 2013; 15(1):46-61. PMC: 4303448. DOI: 10.1002/embr.201337983. View

16.

Drube S, Weber F, Loschinski R, Beyer M, Rothe M, Rabenhorst A . Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells. Oncotarget. 2015; 6(7):5354-68. PMC: 4467154. DOI: 10.18632/oncotarget.3022. View

17.

Tao W, Li P, Shen Z, Shu Y, Liu S . Effects of omega-3 fatty acid nutrition on mortality in septic patients: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2016; 16(1):39. PMC: 4950703. DOI: 10.1186/s12871-016-0200-7. View

18.

Leaver S, Evans T . Acute respiratory distress syndrome. BMJ. 2007; 335(7616):389-94. PMC: 1952500. DOI: 10.1136/bmj.39293.624699.AD. View

19.

Metcalf D, Begley C, Johnson G, Nicola N, Lopez A, Williamson D . Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood. 1986; 68(1):46-57. View

20.

Hapel A, Fung M, Johnson R, Young I, Johnson G, Metcalf D . Biologic properties of molecularly cloned and expressed murine interleukin-3. Blood. 1985; 65(6):1453-9. View