Administration of antisense phosphorothioate oligonucleotide to the p65 subunit of NF-κB inhibits established asthmatic reaction in mice

Choi, Il‐Whan; Kim, Dae‐Ki; Ko, Hyun-Mi; Lee, Hern-Ku

doi:10.1016/j.intimp.2004.07.030

Cited by 72 publications

(47 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various strategies targeted at the NF-kB signaling pathway, such as NF-kB-specific decoy oligonucleotide (19), p65-specific antisense oligonucleotide (20), and IKKb-selective small molecule inhibitor (21), have demonstrated beneficial effects in experimental asthma models. Rip2 is not only a transcriptional product of NF-kB, but also a positive regulator of NF-kB activity (12).…”

Section: Discussionmentioning

confidence: 99%

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Goh

Cook

Upton

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

Persistent activation of NF-κB has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-κB activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-κB 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-1β, 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 IκBα 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-κB activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma.

show abstract

Section: Discussionmentioning

confidence: 99%

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Goh

Cook

Upton

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…47,48 Because TNF-α expression preceded increases in SP-D levels during the allergic airway response, we tested whether this cytokine can contribute to upregulation of SP-D production without allergic sensitization. Interestingly, mice specifically overexpressing TNF-α in alveolar type II cells [43][44][45] had increased SP-D levels.…”

Section: Discussionmentioning

confidence: 99%

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

Hortobagyi

Kierstein

Krytska

et al. 2008

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…The pellet was resuspended in PBS, and cytospin preparations of BAL cells were stained with DiffQuik (International Reagents Corp., Kobe, Japan). Approximately 400 cells were counted in each of 4 different random locations [20].…”

Section: Bronchoalveolar Lavage (Bal) and Cell Countingmentioning

confidence: 99%

Investigation of the Antiasthmatic Properties of Ethanol Extract of <i>Callophyllis japonica</i> in Mice

Park¹,

Lee²,

Chun³

et al. 2014

Trop. J. Pharm Res

View full text Add to dashboard Cite

Administration of antisense phosphorothioate oligonucleotide to the p65 subunit of NF-κB inhibits established asthmatic reaction in mice

Cited by 72 publications

References 33 publications

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Surfactant protein D inhibits TNF-α production by macrophages and dendritic cells in mice

Investigation of the Antiasthmatic Properties of Ethanol Extract of <i>Callophyllis japonica</i> in Mice

Contact Info

Product

Resources

About