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IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures

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@article{3cd4f0a26d674951a2849ab32ca45b29,
title = "IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures",
abstract = "The IL-1 family members IL-1β, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood donors, and reactivated in the presence of IL-1β, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1β, both contributing to amplify production of IL-5, IL-13, and IFN-γ. IL-18 or IL-33 stimulation of Th1 cultures resulted in increased IFN-γ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Rα, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33 had an increased IL-5 secretion. Interestingly, E4BP4 gene expression and the percentage of E4BP4(+) cells of the recently shown IL-10 transcriptional regulator E4BP4 correlated with IL-10 gene expression and protein secretion in Th1 cultures. Taken together, we report that the IL-1 family {"}alarmins{"} IL-18 and IL-33 in addition to amplifying both Th1- and Th2-associated cytokines block production of the regulatory cytokine IL-10 in Th1 cultures.",
keywords = "Cell Differentiation, Cells, Cultured, Cytokines, Humans, Inflammation, Interleukin-10, Interleukin-18, Interleukins, Multigene Family, Suppression, Genetic, Th1 Cells, Th2 Cells, Up-Regulation",
author = "Lars Blom and Poulsen, {Lars K}",
year = "2012",
doi = "10.4049/jimmunol.1103685",
language = "English",
volume = "189",
pages = "4331--7",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

RIS

TY - JOUR

T1 - IL-1 family members IL-18 and IL-33 upregulate the inflammatory potential of differentiated human Th1 and Th2 cultures

AU - Blom, Lars

AU - Poulsen, Lars K

PY - 2012

Y1 - 2012

N2 - The IL-1 family members IL-1β, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood donors, and reactivated in the presence of IL-1β, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1β, both contributing to amplify production of IL-5, IL-13, and IFN-γ. IL-18 or IL-33 stimulation of Th1 cultures resulted in increased IFN-γ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Rα, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33 had an increased IL-5 secretion. Interestingly, E4BP4 gene expression and the percentage of E4BP4(+) cells of the recently shown IL-10 transcriptional regulator E4BP4 correlated with IL-10 gene expression and protein secretion in Th1 cultures. Taken together, we report that the IL-1 family "alarmins" IL-18 and IL-33 in addition to amplifying both Th1- and Th2-associated cytokines block production of the regulatory cytokine IL-10 in Th1 cultures.

AB - The IL-1 family members IL-1β, IL-18, and IL-33 are potent cytokines in relationship to amplifying the CD4(+) T cell cytokine production. To evaluate their impact on in vitro-differentiated human Th1 and Th2 cultures, such cultures were established from naive T cells, purified from healthy blood donors, and reactivated in the presence of IL-1β, IL-18, or IL-33. Interestingly, we observe modifying responses in Th1 and Th2 cultures induced by IL-18 or IL-33 but not by IL-1β, both contributing to amplify production of IL-5, IL-13, and IFN-γ. IL-18 or IL-33 stimulation of Th1 cultures resulted in increased IFN-γ and IL-13 production concurrent with reduced IL-10 gene transcription and secretion even though Th1 cultures, in contrast to IL-18Rα, had low ST2L expression. Furthermore, adding IL-18 to Th1 cultures promoted Tbet mRNA expression and production. Th2 cultures stimulated with IL-18 or IL-33 had an increased IL-5 secretion. Interestingly, E4BP4 gene expression and the percentage of E4BP4(+) cells of the recently shown IL-10 transcriptional regulator E4BP4 correlated with IL-10 gene expression and protein secretion in Th1 cultures. Taken together, we report that the IL-1 family "alarmins" IL-18 and IL-33 in addition to amplifying both Th1- and Th2-associated cytokines block production of the regulatory cytokine IL-10 in Th1 cultures.

KW - Cell Differentiation

KW - Cells, Cultured

KW - Cytokines

KW - Humans

KW - Inflammation

KW - Interleukin-10

KW - Interleukin-18

KW - Interleukins

KW - Multigene Family

KW - Suppression, Genetic

KW - Th1 Cells

KW - Th2 Cells

KW - Up-Regulation

U2 - 10.4049/jimmunol.1103685

DO - 10.4049/jimmunol.1103685

M3 - Journal article

VL - 189

SP - 4331

EP - 4337

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -

ID: 36816495