- Title
- A selective a7 nicotinic acetylcholine receptor agonist, PNU-282987, attenuates ILC2s activation and alternaria-induced airway inflammation
- Creator
- Yuan, Fang; Jiang, Lili; Yang, Ming; Li, Fuguang; Li, Qianyang; Sokulsky, Leon; Wanyan, Yuanyuan; Wang, Lingli; Liu, Xiaojie; Zhou, Lujia; Tay, Hock L.; Zhang, Guojun
- Relation
- Frontiers in Immunology Vol. 11, Issue 1 February 2021, no. 598165
- Publisher Link
- http://dx.doi.org/10.3389/fimmu.2020.598165
- Publisher
- Frontiers Research Foundation
- Resource Type
- journal article
- Date
- 2021
- Description
- Background: The anti-inflammatory effect of an a7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987 on type 2 innate lymphoid cells (ILC2s)-mediated allergic airway inflammation has not yet been established. Aims: To determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33– or Alternaria Alternata (AA)– induced airway inflammation. Methods: PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published a7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-kB were also determined. Results: PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-kB phosphorylation in the PNU-282987–treated group when compared to the GTS-21–treated ILC2s. Conclusion: PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.
- Subject
- type 2 innate lymphoid cells; airway; inflammation; nicotinic acetylcholine receptor; alternaria
- Identifier
- http://hdl.handle.net/1959.13/1461827
- Identifier
- uon:46307
- Identifier
- ISSN:1664-3224
- Language
- eng
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