| First Author | Goh FY | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 5 | Pages | 2691-9 |
| PubMed ID | 23918989 | Mgi Jnum | J:205794 |
| Mgi Id | MGI:5546461 | Doi | 10.4049/jimmunol.1202416 |
| Citation | Goh FY, et al. (2013) Receptor-interacting protein 2 gene silencing attenuates allergic airway inflammation. J Immunol 191(5):2691-9 |
| abstractText | Persistent activation of NF-kappaB has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-kappaB activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-kappaB 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-1beta, 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 IkappaBalpha 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-kappaB activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma. |
