Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo.
Role of nicotinic receptors and acetylcholine in mucous cell metaplasia, hyperplasia, and airway mucus formation in vitro and in vivo.
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DOI：
10.1016/j.jaci.2012.04.002
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发表时间：
2012-09
影响因子：
14.2
通讯作者：
Sopori, Mohan L.
中科院分区：
文献类型：
--
作者：
Gundavarapu, Sravanthi;Wilder, Julie A.;Mishra, Neerad C.;Rir-sima-ah, Jules;Langley, Raymond J.;Singh, Shashi P.;Saeed, Ali Imran;Jaramillo, Richard J.;Gott, Katherine M.;Pena-Philippides, Juan Carlos;Harrod, Kevin S.;McIntosh, J. Michael;Buch, Shilpa;Sopori, Mohan L.
关键词：
气道粘液分泌过多是许多肺部疾病的关键病理生理学特征。香烟烟雾/尼古丁和过敏原是气道粘液的强烈刺激物；然而，粘液调节的机制尚不清楚。描述香烟烟雾/尼古丁调节气道粘液的途径，并确定减少气道粘液的药物。 IL-13 和 γ-氨基丁酸受体 (GABAAR) 与气道粘液有关。我们研究了 IL-13 和 GABAAR 在正常人支气管上皮 (NHBE) 和 A549 细胞中尼古丁诱导的粘液形成以及二手烟烟雾和/或卵清蛋白诱导的体内粘液形成中的作用。尼古丁促进 NHBE 细胞粘液形成；然而，尼古丁诱导的粘液形成不依赖于 IL-13，但对 GABAAR 拮抗剂印防己毒素 (PIC) 敏感。气道上皮细胞表达 α7/α9/α10 烟碱乙酰胆碱受体 (nAChR)，特异性抑制或敲低 α7-（而非 α9/α10-nAChR）可消除响应尼古丁和 IL-13 的粘液形成。此外，添加乙酰胆碱或抑制其降解会增加 NHBE 细胞中的粘液。烟碱受体拮抗剂而非毒蕈碱受体拮抗剂可阻断 NHBE 细胞和/或小鼠气道中过敏原或尼古丁/香烟烟雾诱导的气道粘液形成。尼古丁诱导的气道粘液形成独立于 IL-13，并且 α7-nAChR 在气道粘液细胞化生/增生以及响应各种促粘液剂（包括 IL-13）的粘液产生中至关重要。在没有尼古丁的情况下，乙酰胆碱可能是 α7-nAChR 的生物配体，触发气道粘液形成。在 MUC5AC 通路中，α7-nAChR 位于 IL-13 下游，但位于 GABAARα2 上游。乙酰胆碱和 α-7-nAChR 可作为控制气道粘液的治疗靶点。
Airway mucus hypersecretion is a key pathophysiological feature in number of lung diseases. Cigarette smoke/nicotine and allergens are strong stimulators of airway mucus; however, the mechanism of mucus modulation is unclear. Characterize the pathway by which cigarette smoke/nicotine regulates airway mucus and identify agents that decrease airway mucus. IL-13 and gamma-aminobutyric acid receptors (GABAARs) are implicated in airway mucus. We examined the role of IL-13 and GABAARs in nicotine-induced mucus formation in normal human bronchial epithelial (NHBE) and A549 cells, and secondhand cigarette smoke and/or ovalbumin-induced mucus formation in vivo. Nicotine promotes mucus formation in NHBE cells; however, the nicotine-induced mucus formation is independent of IL-13 but sensitive to the GABAAR antagonist picrotoxin (PIC). Airway epithelial cells express α7/α9/α10 nicotinic acetylcholine receptors (nAChRs) and specific inhibition or knockdown of α7- but not α9/α10-nAChRs abrogates mucus formation in response to nicotine and IL-13. Moreover, addition of acetylcholine or inhibition of its degradation increases mucus in NHBE cells. Nicotinic but not muscarinic receptor antagonists block allergen or nicotine/cigarette smoke-induced airway mucus formation in NHBE cells and/or in mouse airways. Nicotine-induced airway mucus formation is independent of IL-13 and α7-nAChRs are critical in airway mucous cell metaplasia/hyperplasia and mucus production in response to various pro-mucoid agents, including IL-13. In the absence of nicotine, acetylcholine may be the biological ligand for α7-nAChRs to trigger airway mucus formation. α7-nAChRs are downstream of IL-13 but upstream of GABAARα2 in the MUC5AC pathway. Acetylcholine and α-7-nAChRs may serve as therapeutic targets to control airway mucus.
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影响因子：
6.1
作者：
Lips, Katrin S.;Luehrmann, Anke;Kummer, Wolfgang
通讯作者：
Kummer, Wolfgang
DOI：
10.4049/jimmunol.0902227
发表时间：
2010-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mishra NC;Rir-sima-ah J;Boyd RT;Singh SP;Gundavarapu S;Langley RJ;Razani-Boroujerdi S;Sopori ML
通讯作者：
Sopori ML
影响因子：
5.5
作者：
Fucile, S;Sucapane, A;Eusebi, F
通讯作者：
Eusebi, F
DOI：
10.1165/rcmb.2010-0109oc
发表时间：
2011-02-01
影响因子：
6.4
作者：
Fu, Xiao Wen;Wood, Kelsey;Spindel, Eliot R.
通讯作者：
Spindel, Eliot R.
影响因子：
2.9
作者：
Ellison, M;Haberlandt, C;Olivera, BM
通讯作者：
Olivera, BM