Casp8p41 expression in primary T cells induces a proinflammatory response

Julie A. Taylor, Nathan W Cummins, Gary D. Bren, Stacey Rizza, Christopher P. Kolbert, Marshall D. Behrens, Keith L Knutson, Jane C. Kahl, Yan Asmann, Andrew David Badley

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

OBJECTIVE: HIV infection of CD4 T cells can lead to HIV protease-mediated cleavage of procaspase 8 generating a novel, HIV-specific peptide called Casp8p41. Casp8p41 has at least two biologic functions: induction of cell death via mitochondrial depolarization and release of cytochrome C, as well as activation of nuclear factor kappa B (NFκB). We have previously shown that Casp8p41-induced NFκB activation enhances HIV LTR transcription and consequently increases HIV replication. Herein, we questioned whether Casp8p41-induced NFκB activation impacts the cytokine profile of cells expressing Casp8p41. DESIGN: Analysis of cells expressing Casp8p41 and HIV-infected T cells. METHODS: We assessed whether host genes are transcriptionally activated following Casp8p41 production, using microarray analysis, cytokine quantification, followed by western blot and flow cytometry. RESULTS: Microarray analysis identified 259 genes significantly upregulated following expression of Casp8p41. Furthermore, Casp8p41 expression in primary CD4 T cells results in increased production of interleukin (IL)-2, IL-15 and tumor necrosis factor (TNF), as well as IL-1RA; whereas levels of granulocyte macrophage colony-stimulating factor and interferon (IFN)-γ were reduced in the Casp8p41 expressing cells. Intracellular flow cytometry confirmed the co-association of Casp8p41 with elevated TNF in HIV-infected cells. CONCLUSION: These data indicate that the expression of Casp8p41 in HIV-infected CD4 T cells in addition to promoting apoptosis and enhancing HIV replication also promotes a proinflammatory cytokine milieu, which is characteristic of untreated HIV infection.

Original languageEnglish (US)
Pages (from-to)1251-1258
Number of pages8
JournalAIDS
Volume24
Issue number9
DOIs
StatePublished - Jun 1 2010

Fingerprint

HIV
T-Lymphocytes
NF-kappa B
Microarray Analysis
Cytokines
HIV Infections
Flow Cytometry
Tumor Necrosis Factor-alpha
HIV Protease
Interleukin-15
Caspase 8
Interleukins
Cytochromes
Granulocyte-Macrophage Colony-Stimulating Factor
Interferons
Genes
Interleukin-2
Cell Death
Western Blotting
Apoptosis

Keywords

  • Apoptosis
  • Casp8p41
  • HIV
  • Inflammation
  • Protease
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Casp8p41 expression in primary T cells induces a proinflammatory response. / Taylor, Julie A.; Cummins, Nathan W; Bren, Gary D.; Rizza, Stacey; Kolbert, Christopher P.; Behrens, Marshall D.; Knutson, Keith L; Kahl, Jane C.; Asmann, Yan; Badley, Andrew David.

In: AIDS, Vol. 24, No. 9, 01.06.2010, p. 1251-1258.

Research output: Contribution to journalArticle

Taylor, Julie A. ; Cummins, Nathan W ; Bren, Gary D. ; Rizza, Stacey ; Kolbert, Christopher P. ; Behrens, Marshall D. ; Knutson, Keith L ; Kahl, Jane C. ; Asmann, Yan ; Badley, Andrew David. / Casp8p41 expression in primary T cells induces a proinflammatory response. In: AIDS. 2010 ; Vol. 24, No. 9. pp. 1251-1258.
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abstract = "OBJECTIVE: HIV infection of CD4 T cells can lead to HIV protease-mediated cleavage of procaspase 8 generating a novel, HIV-specific peptide called Casp8p41. Casp8p41 has at least two biologic functions: induction of cell death via mitochondrial depolarization and release of cytochrome C, as well as activation of nuclear factor kappa B (NFκB). We have previously shown that Casp8p41-induced NFκB activation enhances HIV LTR transcription and consequently increases HIV replication. Herein, we questioned whether Casp8p41-induced NFκB activation impacts the cytokine profile of cells expressing Casp8p41. DESIGN: Analysis of cells expressing Casp8p41 and HIV-infected T cells. METHODS: We assessed whether host genes are transcriptionally activated following Casp8p41 production, using microarray analysis, cytokine quantification, followed by western blot and flow cytometry. RESULTS: Microarray analysis identified 259 genes significantly upregulated following expression of Casp8p41. Furthermore, Casp8p41 expression in primary CD4 T cells results in increased production of interleukin (IL)-2, IL-15 and tumor necrosis factor (TNF), as well as IL-1RA; whereas levels of granulocyte macrophage colony-stimulating factor and interferon (IFN)-γ were reduced in the Casp8p41 expressing cells. Intracellular flow cytometry confirmed the co-association of Casp8p41 with elevated TNF in HIV-infected cells. CONCLUSION: These data indicate that the expression of Casp8p41 in HIV-infected CD4 T cells in addition to promoting apoptosis and enhancing HIV replication also promotes a proinflammatory cytokine milieu, which is characteristic of untreated HIV infection.",
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T1 - Casp8p41 expression in primary T cells induces a proinflammatory response

AU - Taylor, Julie A.

AU - Cummins, Nathan W

AU - Bren, Gary D.

AU - Rizza, Stacey

AU - Kolbert, Christopher P.

AU - Behrens, Marshall D.

AU - Knutson, Keith L

AU - Kahl, Jane C.

AU - Asmann, Yan

AU - Badley, Andrew David

PY - 2010/6/1

Y1 - 2010/6/1

N2 - OBJECTIVE: HIV infection of CD4 T cells can lead to HIV protease-mediated cleavage of procaspase 8 generating a novel, HIV-specific peptide called Casp8p41. Casp8p41 has at least two biologic functions: induction of cell death via mitochondrial depolarization and release of cytochrome C, as well as activation of nuclear factor kappa B (NFκB). We have previously shown that Casp8p41-induced NFκB activation enhances HIV LTR transcription and consequently increases HIV replication. Herein, we questioned whether Casp8p41-induced NFκB activation impacts the cytokine profile of cells expressing Casp8p41. DESIGN: Analysis of cells expressing Casp8p41 and HIV-infected T cells. METHODS: We assessed whether host genes are transcriptionally activated following Casp8p41 production, using microarray analysis, cytokine quantification, followed by western blot and flow cytometry. RESULTS: Microarray analysis identified 259 genes significantly upregulated following expression of Casp8p41. Furthermore, Casp8p41 expression in primary CD4 T cells results in increased production of interleukin (IL)-2, IL-15 and tumor necrosis factor (TNF), as well as IL-1RA; whereas levels of granulocyte macrophage colony-stimulating factor and interferon (IFN)-γ were reduced in the Casp8p41 expressing cells. Intracellular flow cytometry confirmed the co-association of Casp8p41 with elevated TNF in HIV-infected cells. CONCLUSION: These data indicate that the expression of Casp8p41 in HIV-infected CD4 T cells in addition to promoting apoptosis and enhancing HIV replication also promotes a proinflammatory cytokine milieu, which is characteristic of untreated HIV infection.

AB - OBJECTIVE: HIV infection of CD4 T cells can lead to HIV protease-mediated cleavage of procaspase 8 generating a novel, HIV-specific peptide called Casp8p41. Casp8p41 has at least two biologic functions: induction of cell death via mitochondrial depolarization and release of cytochrome C, as well as activation of nuclear factor kappa B (NFκB). We have previously shown that Casp8p41-induced NFκB activation enhances HIV LTR transcription and consequently increases HIV replication. Herein, we questioned whether Casp8p41-induced NFκB activation impacts the cytokine profile of cells expressing Casp8p41. DESIGN: Analysis of cells expressing Casp8p41 and HIV-infected T cells. METHODS: We assessed whether host genes are transcriptionally activated following Casp8p41 production, using microarray analysis, cytokine quantification, followed by western blot and flow cytometry. RESULTS: Microarray analysis identified 259 genes significantly upregulated following expression of Casp8p41. Furthermore, Casp8p41 expression in primary CD4 T cells results in increased production of interleukin (IL)-2, IL-15 and tumor necrosis factor (TNF), as well as IL-1RA; whereas levels of granulocyte macrophage colony-stimulating factor and interferon (IFN)-γ were reduced in the Casp8p41 expressing cells. Intracellular flow cytometry confirmed the co-association of Casp8p41 with elevated TNF in HIV-infected cells. CONCLUSION: These data indicate that the expression of Casp8p41 in HIV-infected CD4 T cells in addition to promoting apoptosis and enhancing HIV replication also promotes a proinflammatory cytokine milieu, which is characteristic of untreated HIV infection.

KW - Apoptosis

KW - Casp8p41

KW - HIV

KW - Inflammation

KW - Protease

KW - Tumor necrosis factor

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