Reply: To PMID 24084078.
Reply: To PMID 24084078.
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回复:PMID 24084078。
DOI:
10.1016/j.jaci.2014.06.009
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发表时间:
2014
期刊:
影响因子:
--
通讯作者:
Woodfolk,JudithA
中科院分区:
文献类型:
--
作者:
Romeo,MartinJ;Agrawal,Rachana;Pomés,Anna;Woodfolk,JudithA
We would like to thank Dr. Dreyfus for his comment on our review of Th2-promoting cytokine receptors. 1, 2 The objective of our article was to highlight how the molecular features of various forms of these receptors, and their associated components, impacts their function in allergic disease. In particular, we discussed how Th2-promoting cytokines are integral to complex networks owing to their overlapping functions and multiple actions. Such networks undoubtedly conspire to undermine the efficacy of therapeutics designed to target specific molecules. In relation to this point, the concept of using combined therapies in order to attain optimal clinical benefit was mentioned. We agree that extending this notion to include strategies which suppress the expression of genes encoding cytokines and their receptors, or else downstream signaling molecules, might provide an additional weapon in the armory against allergic inflammation.It is important to consider whether experimental evidence supports the ability for gene silencing approaches to effectively suppress Th2-driven allergic inflammation. The papers cited by Dr. Dreyfus describe administration of short interfering RNA (siRNA) to silence IL-13 or STAT6 in vivo using mouse models of OVA-induced airway inflammation. 3, 4 In both models, mice were sensitized intraperitoneally, and then challenged repeatedly with aerosolized or intranasal allergen. Results showed that administration of siRNA prior to each challenge through either intravenous or intranasal routes, ameliorated allergen-induced airway dysfunction or inflammation. However, neither molecule alone inhibited both airway reactivity and infiltrating cells. Moreover, the inhibitory effects observed were incomplete. Indeed, a notable finding in mice treated with IL-13 siRNA was the lack of a reduction in IL-13 levels in bronchoalveolar lavage fluid, despite attenuation of airway hyperresponsiveness. 3 Collectively, these observations underscore not only the pleiotropic and overlapping actions of Th2 cytokines, but also the need for combined therapies directed against multiple targets.
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DOI:
10.1016/j.jaci.2014.06.008
发表时间:
2014
期刊:
The Journal of allergy and clinical immunology
影响因子:
--
作者:
D. Dreyfus
通讯作者:
D. Dreyfus
影响因子:
14.2
作者:
Romeo, Martin J.;Agrawal, Rachana;Pomes, Anna;Woodfolk, Judith A.
通讯作者:
Woodfolk, Judith A.
影响因子:
4.4
作者:
Darcan-Nicolaisen, Yasemin;Meinicke, Holger;Hamelmann, Eckard
通讯作者:
Hamelmann, Eckard
影响因子:
14.2
作者:
T. Lively;K. Kossen;Annette Balhorn;T. Koya;S. Zinnen;K. Takeda;J. Lucas;B. Polisky;Ivan M Richards;E. Gelfand
通讯作者:
E. Gelfand