Expression and alternative processing of IL-18 in human neutrophils

European Journal of Immunology
Susan E RobertsonIain B McInnes

Abstract

Interleukin-18 (IL-18), a member of the IL-1 cytokine superfamily, is an important regulator of both innate and acquired immune responses. We demonstrate here constitutive expression of IL-18 by human neutrophils. Unexpectedly, we observed that neutrophils from peripheral blood or rheumatoid synovial compartments contained not only pro and mature IL-18, but also several novel smaller-molecular-weight IL-18-derived species. Using specific protease inhibitors, and serine protease gene-targeted mice, we demonstrate that these IL-18-derived products arose through caspase-independent cleavage events mediated by the serine proteases, elastase and cathepsin G. Moreover, we report that the net effect of elastase treatment of mature recombinant IL-18 was to reduce its IFN-gamma-inducing activity. Thus, human neutrophils contain IL-18 and IL-18-derived molecular species that can arise through novel enzymatic processing pathways. Through cytosolic, membrane or secretory expression of such processing enzymes, together with generation of IL-18 itself, neutrophils likely play a critical role in regulating IL-18 activities during early innate immune responses.

References

Feb 1, 1989·Infection and Immunity·K NakamuraT Tamura
Apr 1, 1989·Inflammation·C Capodici, R A Berg
Oct 1, 1989·Journal of Interferon Research·S L GoniasJ W Fox
Oct 1, 1993·European Journal of Haematology·N BorregaardD F Bainton
Mar 1, 1997·Journal of Leukocyte Biology·K J LeavellT J Gross
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·A J PurenC A Dinarello
Mar 18, 1999·Journal of Clinical Immunology·G Fantuzzi, C A Dinarello
Jul 10, 1999·Advances in Immunology·M A Cassatella
Nov 24, 1999·The Journal of Clinical Investigation·J A GracieI B McInnes
Feb 29, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M G NeteaC A Dinarello
Jun 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·B P LeungF Y Liew
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·E J CampbellC A Owen
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·D G PerregauxC A Gabel
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·X Q WeiF Y Liew
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·S H KimC A Dinarello
May 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·B C SuhK T Kim
Aug 18, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·B P LeungI B McInnes
Nov 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S SugawaraH Takada
Dec 12, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J A JordanP A Ward
Dec 26, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fanny N LauwTom van der Poll
Jan 16, 2002·The Journal of Biological Chemistry·Soo-Hyun KimCharles A Dinarello
Jan 30, 2003·Journal of Leukocyte Biology·J Alastair GracieIain B McInnes
Feb 22, 2003·Infection and Immunity·Xuchu QueSharon L Reed
Jul 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claudio A CanettiClaudio A Cannetti
Mar 9, 2004·Postȩpy higieny i medycyny doświadczalnej·Marek Fol, Teresa Gościcka

❮ Previous
Next ❯

Citations

Feb 19, 2011·Rheumatology International·Hideshi YamazakiShun'ichiro Taniguchi
Dec 1, 2007·Bioinformatics·Michal DraminskiJan Komorowski
Nov 3, 2010·Current Opinion in Hematology·Ulf Meyer-Hoffert, Oliver Wiedow
Sep 17, 2010·Molecular Medicine·Suhail AkhtarMashkoor A Choudhry
May 9, 2014·Molecular Medicine·Laura C O'BrienStefano Toldo
Mar 13, 2016·The American Journal of Pathology·Madalina-Viviana NastaseLiliana Schaefer
Oct 19, 2010·Journal of Leukocyte Biology·Dirk E Smith
Dec 2, 2009·Arthritis and Rheumatism·Monica GumaMaripat Corr
Nov 13, 2009·American Journal of Physiology. Cell Physiology·Christopher C SillimanAnirban Banerjee
Sep 11, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carl F FortinPatrick P McDonald
Mar 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kyung-Eun KimDae-Ho Cho
Jun 12, 2019·Inflammation and Regeneration·Naoe KanekoJunya Masumoto
Jan 9, 2014·The Journal of Biological Chemistry·Martina BakeleDominik Hartl
Jun 19, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rebecca E RiiseFredrik B Thorén
Nov 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Roman SpörriAnnette Oxenius
Sep 5, 2015·Transplant International : Official Journal of the European Society for Organ Transplantation·Haifeng GuXueying Lv
Aug 27, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Roberto PieriniThomas Henry
Jun 14, 2019·Current Opinion in Rheumatology·Giusi PrencipeFabrizio De Benedetti
Dec 23, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emer P ReevesNoel G McElvaney
Mar 13, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicholas S WilsonAvi Ashkenazi
Nov 7, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elena KhanovaHidekazu Tsukamoto
Jul 15, 2015·The American Journal of Pathology·Elodie BousquetYvonne de Kozak
Apr 5, 2011·Joint, Bone, Spine : Revue Du Rhumatisme·Miriam WittmannMichael F McDermott

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.