Silencing of TNF-α receptors coordinately suppresses TNF-α expression through NF-κB activation blockade in THP-1 macrophage

Nandini Verma; Indrajit Chaudhury; Deepak Kumar; Rakha H. Das

doi:10.1016/j.febslet.2009.08.007

Silencing of TNF-α receptors coordinately suppresses TNF-α expression through NF-κB activation blockade in THP-1 macrophage

Nandini Verma, Indrajit Chaudhury, Deepak Kumar, Rakha H. Das

Biochemistry, Molecular Biology, and Biophysics (TMED)

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Persistently elevated level of TNF-α has been implicated in several inflammatory disorders, however, its autocrine production through TNF-α receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-α expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-α induced NF-κB activation to a higher extent. It was further observed that NF-κB inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-α expression. All these results suggest that TNF-α expression is regulated by synergistic signaling of TNF receptors through downstream NF-κB activation.

Original language	English (US)
Pages (from-to)	2968-2974
Number of pages	7
Journal	FEBS Letters
Volume	583
Issue number	17
DOIs	https://doi.org/10.1016/j.febslet.2009.08.007
State	Published - Sep 3 2009

Bibliographical note

Funding Information:
The authors gratefully acknowledge the financial support of the Council of Scientific and Industrial Research (India) to carry out this work. N.V., I.C. and D.K. are recipients of Senior Research Fellowships, respectively, from Council of Scientific and Industrial Research, University Grants Commission and Indian Council Medical Research, India.

Keywords

DNAzyme
NF-κB
TNF-R1
TNF-R2
TNF-α
siRNA

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10.1016/j.febslet.2009.08.007

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title = "Silencing of TNF-α receptors coordinately suppresses TNF-α expression through NF-κB activation blockade in THP-1 macrophage",

abstract = "Persistently elevated level of TNF-α has been implicated in several inflammatory disorders, however, its autocrine production through TNF-α receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-α expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-α induced NF-κB activation to a higher extent. It was further observed that NF-κB inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-α expression. All these results suggest that TNF-α expression is regulated by synergistic signaling of TNF receptors through downstream NF-κB activation.",

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author = "Nandini Verma and Indrajit Chaudhury and Deepak Kumar and Das, {Rakha H.}",

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AU - Verma, Nandini

AU - Chaudhury, Indrajit

AU - Kumar, Deepak

AU - Das, Rakha H.

N1 - Funding Information: The authors gratefully acknowledge the financial support of the Council of Scientific and Industrial Research (India) to carry out this work. N.V., I.C. and D.K. are recipients of Senior Research Fellowships, respectively, from Council of Scientific and Industrial Research, University Grants Commission and Indian Council Medical Research, India.

PY - 2009/9/3

Y1 - 2009/9/3

N2 - Persistently elevated level of TNF-α has been implicated in several inflammatory disorders, however, its autocrine production through TNF-α receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-α expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-α induced NF-κB activation to a higher extent. It was further observed that NF-κB inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-α expression. All these results suggest that TNF-α expression is regulated by synergistic signaling of TNF receptors through downstream NF-κB activation.

AB - Persistently elevated level of TNF-α has been implicated in several inflammatory disorders, however, its autocrine production through TNF-α receptors signaling is poorly understood. Here we report that simultaneous silencing of TNF-receptors, R1 and R2 by DNAzyme or siRNA suppressed TNF-α expression more efficiently than silencing them individually in lipopolysaccharides (LPS) stimulated THP-1 macrophages. Co-silencing of TNF-receptors also inhibited TNF-α induced NF-κB activation to a higher extent. It was further observed that NF-κB inhibitor but not c-Jun N-terminal kinase inhibitor (SP600125) suppressed TNF-α expression. All these results suggest that TNF-α expression is regulated by synergistic signaling of TNF receptors through downstream NF-κB activation.

KW - DNAzyme

KW - NF-κB

KW - TNF-R1

KW - TNF-R2

KW - TNF-α

KW - siRNA

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Silencing of TNF-α receptors coordinately suppresses TNF-α expression through NF-κB activation blockade in THP-1 macrophage

Abstract

Bibliographical note

Keywords

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