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  1. Article ; Online: Assessing Interleukin-1β Activation During Pyroptosis.

    LaRock, Doris L / LaRock, Christopher N

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2641, Page(s) 163–169

    Abstract: The cytokine interleukin-1β (IL-1β) is a major mediator of inflammation in autoinflammatory disease and the host response to infection. IL-1β is stored within cells in an inert form, which requires proteolytic removal of an amino-terminal fragment in ... ...

    Abstract The cytokine interleukin-1β (IL-1β) is a major mediator of inflammation in autoinflammatory disease and the host response to infection. IL-1β is stored within cells in an inert form, which requires proteolytic removal of an amino-terminal fragment in order to bind the IL-1 receptor complex and have pro-inflammatory activity. This cleavage event is canonically carried out by inflammasome-activated caspase proteases, but microbe and host proteases can also generate unique active forms. Post-translational regulation of IL-1β and the diversity in resulting products can present challenges to the evaluation of IL-1β activation. This chapter details methods and important controls for the accurate and sensitive measurement of IL-1β activation within biological samples.
    MeSH term(s) Pyroptosis/physiology ; Interleukin-1beta/metabolism ; Inflammasomes/metabolism ; Caspases ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Caspase 1/metabolism
    Chemical Substances Interleukin-1beta ; Inflammasomes ; Caspases (EC 3.4.22.-) ; NLR Family, Pyrin Domain-Containing 3 Protein ; Caspase 1 (EC 3.4.22.36)
    Language English
    Publishing date 2023-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3040-2_13
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Improved Methodology for Evaluating Nanomedicine Antibacterial Properties in Biological Fluids.

    Ashkarran, Ali Akbar / Sharifi, Shahriar / LaRock, Christopher N / Mahmoudi, Morteza

    ACS pharmacology & translational science

    2024  Volume 7, Issue 3, Page(s) 855–862

    Abstract: Accurate assessment of nanomedicines' antibacterial properties is pivotal for their effective use in ... ...

    Abstract Accurate assessment of nanomedicines' antibacterial properties is pivotal for their effective use in both
    Language English
    Publishing date 2024-02-13
    Publishing country United States
    Document type Journal Article
    ISSN 2575-9108
    ISSN (online) 2575-9108
    DOI 10.1021/acsptsci.3c00348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Antibiotic Treatment, Mechanisms for Failure, and Adjunctive Therapies for Infections by Group A

    Johnson, Anders F / LaRock, Christopher N

    Frontiers in microbiology

    2021  Volume 12, Page(s) 760255

    Abstract: ... Group ... ...

    Abstract Group A
    Language English
    Publishing date 2021-11-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.760255
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Constitutive secretion of pro-IL-18 allows keratinocytes to initiate inflammation during bacterial infection.

    Johnson, Anders F / Sands, Jenna S / Trivedi, Keya M / Russell, Raedeen / LaRock, Doris L / LaRock, Christopher N

    PLoS pathogens

    2023  Volume 19, Issue 4, Page(s) e1011321

    Abstract: Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to ...

    Abstract Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to pathogen invasion. Here, we characterized the proinflammatory cytokine repertoire produced by primary human keratinocytes and surrogate cell lines commonly used in vitro. Infection induces several cytokines and chemokines, but keratinocytes constitutively secrete IL-18 in a form that is inert (pro-IL-18) and lacks proinflammatory activity. Canonically, IL-18 activation and secretion are coupled through a single proteolytic event that is regulated intracellularly by the inflammasome protease caspase-1 in myeloid cells. The pool of extracellular pro-IL-18 generated by keratinocytes is poised to sense extracellular proteases. It is directly processed into a mature active form by SpeB, a secreted GAS protease that is a critical virulent factor during skin infection. This mechanism contributes to the proinflammatory response against GAS, resulting in T cell activation and the secretion of IFN-γ. Under these conditions, isolates of several other major bacterial pathogens and microbiota of the skin were found to not have significant IL-18-maturing ability. These results suggest keratinocyte-secreted IL-18 is a sentinel that sounds an early alarm that is highly sensitive to GAS, yet tolerant to non-invasive members of the microbiota.
    MeSH term(s) Humans ; Bacterial Infections/metabolism ; Cytokines/metabolism ; Inflammation ; Interleukin-18/metabolism ; Keratinocytes/metabolism ; Peptide Hydrolases/metabolism
    Chemical Substances Cytokines ; Interleukin-18 ; Peptide Hydrolases (EC 3.4.-) ; IL18 protein, human
    Language English
    Publishing date 2023-04-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011321
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Playing With Fire: Proinflammatory Virulence Mechanisms of Group A

    Wilde, Shyra / Johnson, Anders F / LaRock, Christopher N

    Frontiers in cellular and infection microbiology

    2021  Volume 11, Page(s) 704099

    Abstract: ... Group ... ...

    Abstract Group A
    MeSH term(s) Humans ; Shock, Septic ; Streptococcal Infections ; Streptococcus pyogenes ; Virulence ; Virulence Factors
    Chemical Substances Virulence Factors
    Language English
    Publishing date 2021-07-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.704099
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Group A Streptococcus induces GSDMA-dependent pyroptosis in keratinocytes.

    LaRock, Doris L / Johnson, Anders F / Wilde, Shyra / Sands, Jenna S / Monteiro, Marcos P / LaRock, Christopher N

    Nature

    2022  Volume 605, Issue 7910, Page(s) 527–531

    Abstract: Gasdermins (GSDMs) are a family of pore-forming effectors that permeabilize the cell membrane during the cell death program ... ...

    Abstract Gasdermins (GSDMs) are a family of pore-forming effectors that permeabilize the cell membrane during the cell death program pyroptosis
    MeSH term(s) Animals ; Caspases ; Keratinocytes ; Mice ; Pore Forming Cytotoxic Proteins ; Pyroptosis ; Streptococcus pyogenes/metabolism ; Streptococcus pyogenes/pathogenicity ; Virulence ; Virulence Factors
    Chemical Substances Pore Forming Cytotoxic Proteins ; Virulence Factors ; Caspases (EC 3.4.22.-)
    Language English
    Publishing date 2022-05-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-04717-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 26: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

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  7. Article ; Online: Constitutive secretion of pro-IL-18 allows keratinocytes to initiate inflammation during bacterial infection.

    Anders F Johnson / Jenna S Sands / Keya M Trivedi / Raedeen Russell / Doris L LaRock / Christopher N LaRock

    PLoS Pathogens, Vol 19, Iss 4, p e

    2023  Volume 1011321

    Abstract: Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to ...

    Abstract Group A Streptococcus (GAS, Streptococcus pyogenes) is a professional human pathogen that commonly infects the skin. Keratinocytes are one of the first cells to contact GAS, and by inducing inflammation, they can initiate the earliest immune responses to pathogen invasion. Here, we characterized the proinflammatory cytokine repertoire produced by primary human keratinocytes and surrogate cell lines commonly used in vitro. Infection induces several cytokines and chemokines, but keratinocytes constitutively secrete IL-18 in a form that is inert (pro-IL-18) and lacks proinflammatory activity. Canonically, IL-18 activation and secretion are coupled through a single proteolytic event that is regulated intracellularly by the inflammasome protease caspase-1 in myeloid cells. The pool of extracellular pro-IL-18 generated by keratinocytes is poised to sense extracellular proteases. It is directly processed into a mature active form by SpeB, a secreted GAS protease that is a critical virulent factor during skin infection. This mechanism contributes to the proinflammatory response against GAS, resulting in T cell activation and the secretion of IFN-γ. Under these conditions, isolates of several other major bacterial pathogens and microbiota of the skin were found to not have significant IL-18-maturing ability. These results suggest keratinocyte-secreted IL-18 is a sentinel that sounds an early alarm that is highly sensitive to GAS, yet tolerant to non-invasive members of the microbiota.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Detoxification of reactive oxygen species by the hyaluronic acid capsule of group A

    Wilde, Shyra / Dash, Ananya / Johnson, Anders / Mackey, Kialani / Okumura, Cheryl Y M / LaRock, Christopher N

    Infection and immunity

    2023  Volume 91, Issue 11, Page(s) e0025823

    Abstract: The pro-inflammatory cytokine IL-6 regulates antimicrobial responses that are broadly crucial in the defense against infection. Our prior work shows that IL-6 promotes the killing of the M4 serotype group ... ...

    Abstract The pro-inflammatory cytokine IL-6 regulates antimicrobial responses that are broadly crucial in the defense against infection. Our prior work shows that IL-6 promotes the killing of the M4 serotype group A
    MeSH term(s) Animals ; Mice ; Reactive Oxygen Species ; Hyaluronic Acid ; Antioxidants ; Interleukin-6 ; Neutrophils/microbiology ; Streptococcus pyogenes ; Streptococcal Infections/microbiology ; Bacterial Proteins
    Chemical Substances Reactive Oxygen Species ; Hyaluronic Acid (9004-61-9) ; Antioxidants ; Interleukin-6 ; Bacterial Proteins
    Language English
    Publishing date 2023-10-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/iai.00258-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 684: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Group A Streptococcus Infection of the Nasopharynx Requires Proinflammatory Signaling through the Interleukin-1 Receptor.

    LaRock, Doris L / Russell, Raedeen / Johnson, Anders F / Wilde, Shyra / LaRock, Christopher N

    Infection and immunity

    2020  Volume 88, Issue 10

    Abstract: ... Group ... ...

    Abstract Group A
    MeSH term(s) Animals ; Anti-Bacterial Agents/adverse effects ; Bacterial Proteins/genetics ; Bacterial Proteins/immunology ; Caspase 1/genetics ; Caspase 1/immunology ; Chemotaxis, Leukocyte ; Exotoxins/genetics ; Exotoxins/immunology ; Inflammation ; Interleukin 1 Receptor Antagonist Protein/pharmacology ; Interleukin-1beta/immunology ; Mice ; Nasopharynx/immunology ; Nasopharynx/microbiology ; Neutrophils/immunology ; Pharyngitis/genetics ; Pharyngitis/immunology ; Pharyngitis/microbiology ; Receptors, Interleukin-1 Type I/genetics ; Receptors, Interleukin-1 Type I/immunology ; Signal Transduction/drug effects ; Signal Transduction/immunology ; Streptococcal Infections/genetics ; Streptococcal Infections/immunology ; Streptococcal Infections/microbiology ; Streptococcus pyogenes/drug effects ; Streptococcus pyogenes/genetics ; Streptococcus pyogenes/growth & development ; Streptococcus pyogenes/pathogenicity ; Virulence/drug effects ; Virulence/genetics
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Exotoxins ; IL1B protein, mouse ; IL1R1 protein, mouse ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-1beta ; Receptors, Interleukin-1 Type I ; erythrogenic toxin ; Casp1 protein, mouse (EC 3.4.22.36) ; Caspase 1 (EC 3.4.22.36)
    Language English
    Publishing date 2020-09-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00356-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 684: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  10. Article ; Online: Chemical Optimization of Selective

    Everett, Martin J / Davies, David T / Leiris, Simon / Sprynski, Nicolas / Llanos, Agustina / Castandet, Jérôme M / Lozano, Clarisse / LaRock, Christopher N / LaRock, Doris L / Corsica, Giuseppina / Docquier, Jean-Denis / Pallin, Thomas D / Cridland, Andrew / Blench, Toby / Zalacain, Magdalena / Lemonnier, Marc

    ACS infectious diseases

    2023  Volume 9, Issue 2, Page(s) 270–282

    Abstract: LasB elastase is a broad-spectrum exoprotease and a key virulence factor ... ...

    Abstract LasB elastase is a broad-spectrum exoprotease and a key virulence factor of
    MeSH term(s) Animals ; Mice ; Kinetics ; Models, Animal ; Pancreatic Elastase ; Pseudomonas aeruginosa ; Virulence Factors
    Chemical Substances Pancreatic Elastase (EC 3.4.21.36) ; Virulence Factors ; IL1B protein, mouse
    Language English
    Publishing date 2023-01-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.2c00418
    Database MEDical Literature Analysis and Retrieval System OnLINE

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