Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing
- Author
- Danielle Clancy (UGent) , Graeme P. Sullivan, Hannah B. T. Moran, Conor M. Henry, Emer P. Reeves, Noel G. McElvaney, Ed C. Lavelle and Seamus J. Martin
- Organization
- Abstract
- Neutrophil granule proteases are thought to function as anti-microbial effectors, cooperatively hydrolyzing microorganisms within phagosomes, or upon deployment into the extracellular space. However, evidence also suggests that neutrophil proteases play an important role in the coordination and escalation of inflammatory reactions, but how this is achieved has been obscure. IL-1 family cytokines are important initiators of inflammation and are typically released via necrosis but require proteolytic processing for activation. Here, we show that proteases liberated from activated neutrophils can positively or negatively regulate the activity of six IL-1 family cytokines (IL-1 alpha, IL-1 beta, IL-33, IL-36 alpha, IL-36 beta, and IL-36 gamma) with exquisite sensitivity. In contrast, extracellular neutrophil proteases displayed very poor bactericidal activity, exhibiting 100-fold greater potency toward cytokine processing than bacterial killing. Thus, in addition to their classical role as phagocytes, neutrophils play an important immunoregulatory role through deployment of their granule proteases into the extracellular space to process multiple IL-1 family cytokines.
- Keywords
- PAPILLON-LEFEVRE-SYNDROME, SERINE PROTEASES, INFLAMMATORY RESPONSE, FAMILY CYTOKINES, CELL-DEATH, INTERLEUKIN-1-BETA, ELASTASE, PROTEOLYSIS, ACTIVATION, CLEAVAGE
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8727852
- MLA
- Clancy, Danielle, et al. “Extracellular Neutrophil Proteases Are Efficient Regulators of IL-1, IL-33, and IL-36 Cytokine Activity but Poor Effectors of Microbial Killing.” CELL REPORTS, vol. 22, no. 11, 2018, pp. 2937–50, doi:10.1016/j.celrep.2018.02.062.
- APA
- Clancy, D., Sullivan, G. P., Moran, H. B. T., Henry, C. M., Reeves, E. P., McElvaney, N. G., … Martin, S. J. (2018). Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing. CELL REPORTS, 22(11), 2937–2950. https://doi.org/10.1016/j.celrep.2018.02.062
- Chicago author-date
- Clancy, Danielle, Graeme P. Sullivan, Hannah B. T. Moran, Conor M. Henry, Emer P. Reeves, Noel G. McElvaney, Ed C. Lavelle, and Seamus J. Martin. 2018. “Extracellular Neutrophil Proteases Are Efficient Regulators of IL-1, IL-33, and IL-36 Cytokine Activity but Poor Effectors of Microbial Killing.” CELL REPORTS 22 (11): 2937–50. https://doi.org/10.1016/j.celrep.2018.02.062.
- Chicago author-date (all authors)
- Clancy, Danielle, Graeme P. Sullivan, Hannah B. T. Moran, Conor M. Henry, Emer P. Reeves, Noel G. McElvaney, Ed C. Lavelle, and Seamus J. Martin. 2018. “Extracellular Neutrophil Proteases Are Efficient Regulators of IL-1, IL-33, and IL-36 Cytokine Activity but Poor Effectors of Microbial Killing.” CELL REPORTS 22 (11): 2937–2950. doi:10.1016/j.celrep.2018.02.062.
- Vancouver
- 1.Clancy D, Sullivan GP, Moran HBT, Henry CM, Reeves EP, McElvaney NG, et al. Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing. CELL REPORTS. 2018;22(11):2937–50.
- IEEE
- [1]D. Clancy et al., “Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing,” CELL REPORTS, vol. 22, no. 11, pp. 2937–2950, 2018.
@article{8727852,
abstract = {{Neutrophil granule proteases are thought to function as anti-microbial effectors, cooperatively hydrolyzing microorganisms within phagosomes, or upon deployment into the extracellular space. However, evidence also suggests that neutrophil proteases play an important role in the coordination and escalation of inflammatory reactions, but how this is achieved has been obscure. IL-1 family cytokines are important initiators of inflammation and are typically released via necrosis but require proteolytic processing for activation. Here, we show that proteases liberated from activated neutrophils can positively or negatively regulate the activity of six IL-1 family cytokines (IL-1 alpha, IL-1 beta, IL-33, IL-36 alpha, IL-36 beta, and IL-36 gamma) with exquisite sensitivity. In contrast, extracellular neutrophil proteases displayed very poor bactericidal activity, exhibiting 100-fold greater potency toward cytokine processing than bacterial killing. Thus, in addition to their classical role as phagocytes, neutrophils play an important immunoregulatory role through deployment of their granule proteases into the extracellular space to process multiple IL-1 family cytokines.}},
author = {{Clancy, Danielle and Sullivan, Graeme P. and Moran, Hannah B. T. and Henry, Conor M. and Reeves, Emer P. and McElvaney, Noel G. and Lavelle, Ed C. and Martin, Seamus J.}},
issn = {{2211-1247}},
journal = {{CELL REPORTS}},
keywords = {{PAPILLON-LEFEVRE-SYNDROME,SERINE PROTEASES,INFLAMMATORY RESPONSE,FAMILY CYTOKINES,CELL-DEATH,INTERLEUKIN-1-BETA,ELASTASE,PROTEOLYSIS,ACTIVATION,CLEAVAGE}},
language = {{eng}},
number = {{11}},
pages = {{2937--2950}},
title = {{Extracellular neutrophil proteases are efficient regulators of IL-1, IL-33, and IL-36 cytokine activity but poor effectors of microbial killing}},
url = {{http://doi.org/10.1016/j.celrep.2018.02.062}},
volume = {{22}},
year = {{2018}},
}
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