Dataset Information

A Selective ?7 Nicotinic Acetylcholine Receptor Agonist, PNU-282987, Attenuates ILC2s Activation and Alternaria-Induced Airway Inflammation.

ABSTRACT:

Background

The anti-inflammatory effect of an ?7nAChR 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 ?7nAChR 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-?B 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-?B 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.

SUBMITTER: Yuan F

PROVIDER: S-EPMC7883686 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

A Selective α7 Nicotinic Acetylcholine Receptor Agonist, PNU-282987, Attenuates ILC2s Activation and <i>Alternaria</i>-Induced Airway Inflammation.

Yuan Fang F Jiang Lili L Li Qianyang Q Sokulsky Leon L Wanyan Yuanyuan Y Wang Lingli L Liu Xiaojie X Zhou Lujia L Tay Hock L HL Zhang Guojun G Yang Ming M Li Fuguang F

Frontiers in immunology 20210201

<h4>Background</h4>The anti-inflammatory effect of an α7nAChR 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.<h4>Aims</h4>To determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33- or <i>Alternaria Alternata</i> (AA)- induced airway inflammation.<h4>Methods</h4>PNU-282987 was administ ...[more]

PMID: 33597946

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