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Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

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Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation. / Goh, Fera Y.; Cook, Katrina L. T. P.; Upton, Nadine; Tao, Lin; Lah, Lin Chin; Leung, Bernard P.; Wong, W. S. Fred.

In: Journal of Immunology, Vol. 191, No. 5, N/A, 01.09.2013, p. 2691-2699.

Research output: Contribution to journalArticle

Harvard

Goh, FY, Cook, KLTP, Upton, N, Tao, L, Lah, LC, Leung, BP & Wong, WSF 2013, 'Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation', Journal of Immunology, vol. 191, no. 5, N/A, pp. 2691-2699. https://doi.org/10.4049/jimmunol.1202416

APA

Goh, F. Y., Cook, K. L. T. P., Upton, N., Tao, L., Lah, L. C., Leung, B. P., & Wong, W. S. F. (2013). Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation. Journal of Immunology, 191(5), 2691-2699. [N/A]. https://doi.org/10.4049/jimmunol.1202416

Vancouver

Goh FY, Cook KLTP, Upton N, Tao L, Lah LC, Leung BP et al. Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation. Journal of Immunology. 2013 Sep 1;191(5):2691-2699. N/A. https://doi.org/10.4049/jimmunol.1202416

Author

Goh, Fera Y. ; Cook, Katrina L. T. P. ; Upton, Nadine ; Tao, Lin ; Lah, Lin Chin ; Leung, Bernard P. ; Wong, W. S. Fred. / Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation. In: Journal of Immunology. 2013 ; Vol. 191, No. 5. pp. 2691-2699.

Bibtex Download

@article{2f00fdc2f4164b3f8b069bcae8e39aeb,
title = "Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation",
abstract = "Persistent activation of NF-kappa B has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-kappa B activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-kappa B activity. We investigated potential protective effects of Rip2 gene silencing using small interfering RNA (siRNA) in an OVA-induced mouse asthma model. Rip2 protein level was found to be upregulated in allergic airway inflammation. A potent and selective Rip2 siRNA given intratracheally knocked down Rip2 expression in OVA-challenged lungs and reduced OVA-induced increases in total and eosinophil counts, and IL-4, IL-5, IL-13, IL-1 beta, IL-33, and eotaxin levels in bronchoalveolar lavage fluid. Rip2 silencing blocked OVA-induced inflammatory cell infiltration and mucus hypersecretion as observed in lung sections, and mRNA expression of ICAM-1, VCAM-1, E-selectin, RANTES, IL-17, IL-33, thymic stromal lymphopoietin, inducible NO synthase, and MUC5ac in lung tissues. In addition, elevation of serum OVA-specific IgE level in mouse asthma model was markedly suppressed by Rip2 siRNA, together with reduced IL-4, IL-5, and IL-13 production in lymph node cultures. Furthermore, Rip2 siRNA-treated mice produced significantly less airway hyperresponsiveness induced by methacholine. Mechanistically, Rip2 siRNA was found to enhance cytosolic level of I kappa B alpha and block p65 nuclear translocation and DNA-binding activity in lung tissues from OVA-challenged mice. Taken together, our findings clearly show that knockdown of Rip2 by gene silencing ameliorates experimental allergic airway inflammation, probably via interruption of NF-kappa B activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma.",
keywords = "NF-KAPPA-B, THYMIC STROMAL LYMPHOPOIETIN, EPITHELIAL-CELLS, SMOOTH-MUSCLE, NITRIC-OXIDE, IMMUNE-SYSTEM, MAST-CELLS, TNF-ALPHA, ASTHMA, ACTIVATION",
author = "Goh, {Fera Y.} and Cook, {Katrina L. T. P.} and Nadine Upton and Lin Tao and Lah, {Lin Chin} and Leung, {Bernard P.} and Wong, {W. S. Fred}",
year = "2013",
month = sep,
day = "1",
doi = "10.4049/jimmunol.1202416",
language = "English",
volume = "191",
pages = "2691--2699",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "5",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

AU - Goh, Fera Y.

AU - Cook, Katrina L. T. P.

AU - Upton, Nadine

AU - Tao, Lin

AU - Lah, Lin Chin

AU - Leung, Bernard P.

AU - Wong, W. S. Fred

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Persistent activation of NF-kappa B has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-kappa B activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-kappa B activity. We investigated potential protective effects of Rip2 gene silencing using small interfering RNA (siRNA) in an OVA-induced mouse asthma model. Rip2 protein level was found to be upregulated in allergic airway inflammation. A potent and selective Rip2 siRNA given intratracheally knocked down Rip2 expression in OVA-challenged lungs and reduced OVA-induced increases in total and eosinophil counts, and IL-4, IL-5, IL-13, IL-1 beta, IL-33, and eotaxin levels in bronchoalveolar lavage fluid. Rip2 silencing blocked OVA-induced inflammatory cell infiltration and mucus hypersecretion as observed in lung sections, and mRNA expression of ICAM-1, VCAM-1, E-selectin, RANTES, IL-17, IL-33, thymic stromal lymphopoietin, inducible NO synthase, and MUC5ac in lung tissues. In addition, elevation of serum OVA-specific IgE level in mouse asthma model was markedly suppressed by Rip2 siRNA, together with reduced IL-4, IL-5, and IL-13 production in lymph node cultures. Furthermore, Rip2 siRNA-treated mice produced significantly less airway hyperresponsiveness induced by methacholine. Mechanistically, Rip2 siRNA was found to enhance cytosolic level of I kappa B alpha and block p65 nuclear translocation and DNA-binding activity in lung tissues from OVA-challenged mice. Taken together, our findings clearly show that knockdown of Rip2 by gene silencing ameliorates experimental allergic airway inflammation, probably via interruption of NF-kappa B activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma.

AB - Persistent activation of NF-kappa B has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-kappa B activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-kappa B activity. We investigated potential protective effects of Rip2 gene silencing using small interfering RNA (siRNA) in an OVA-induced mouse asthma model. Rip2 protein level was found to be upregulated in allergic airway inflammation. A potent and selective Rip2 siRNA given intratracheally knocked down Rip2 expression in OVA-challenged lungs and reduced OVA-induced increases in total and eosinophil counts, and IL-4, IL-5, IL-13, IL-1 beta, IL-33, and eotaxin levels in bronchoalveolar lavage fluid. Rip2 silencing blocked OVA-induced inflammatory cell infiltration and mucus hypersecretion as observed in lung sections, and mRNA expression of ICAM-1, VCAM-1, E-selectin, RANTES, IL-17, IL-33, thymic stromal lymphopoietin, inducible NO synthase, and MUC5ac in lung tissues. In addition, elevation of serum OVA-specific IgE level in mouse asthma model was markedly suppressed by Rip2 siRNA, together with reduced IL-4, IL-5, and IL-13 production in lymph node cultures. Furthermore, Rip2 siRNA-treated mice produced significantly less airway hyperresponsiveness induced by methacholine. Mechanistically, Rip2 siRNA was found to enhance cytosolic level of I kappa B alpha and block p65 nuclear translocation and DNA-binding activity in lung tissues from OVA-challenged mice. Taken together, our findings clearly show that knockdown of Rip2 by gene silencing ameliorates experimental allergic airway inflammation, probably via interruption of NF-kappa B activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma.

KW - NF-KAPPA-B

KW - THYMIC STROMAL LYMPHOPOIETIN

KW - EPITHELIAL-CELLS

KW - SMOOTH-MUSCLE

KW - NITRIC-OXIDE

KW - IMMUNE-SYSTEM

KW - MAST-CELLS

KW - TNF-ALPHA

KW - ASTHMA

KW - ACTIVATION

U2 - 10.4049/jimmunol.1202416

DO - 10.4049/jimmunol.1202416

M3 - Article

VL - 191

SP - 2691

EP - 2699

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 5

M1 - N/A

ER -

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