Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells.
Glucocorticoid Insensitivity in Asthma: The Unique Role for Airway Smooth Muscle Cells.
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DOI：
10.3390/ijms23168966
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发表时间：
2022-08-11
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
尽管大多数有哮喘症状的患者通过吸入糖皮质激素（GCs）能得到良好控制，但仍有一部分重度哮喘患者对GC治疗反应不佳。这种GC不敏感（GCI）给哮喘患者的治疗带来了巨大挑战。尽管已有多个研究小组利用免疫细胞（外周血单个核细胞和肺泡巨噬细胞）对重度哮喘患者的GCI进行了研究，但对于非免疫细胞，如气道平滑肌（ASM）细胞中潜在的分子机制仍不明确。在哮喘中，ASM细胞是GC治疗的靶点之一，实验和临床证据均表明，它不仅是支气管收缩的关键因素，还在气道炎症和重塑中发挥重要作用。在此，我们总结了目前对GC在哮喘中作用/信号传导的认识，特别是GC受体（GR）的“位点特异性磷酸化”及其在调节GC作用中的作用。我们还回顾了研究GCI及与哮喘严重程度相关的炎症介质时常见的一些误区。最后，我们讨论并对比了免疫细胞与非免疫细胞（如ASM细胞）中GC作用受损潜在的分子机制。
Although most patients with asthma symptoms are well controlled by inhaled glucocorticoids (GCs), a subgroup of patients suffering from severe asthma respond poorly to GC therapy. Such GC insensitivity (GCI) represents a profound challenge in managing patients with asthma. Even though GCI in patients with severe asthma has been investigated by several groups using immune cells (peripheral blood mononuclear cells and alveolar macrophages), uncertainty exists regarding the underlying molecular mechanisms in non-immune cells, such as airway smooth cells (ASM) cells. In asthma, ASM cells are among the targets of GC therapy and have emerged as key contributors not only to bronchoconstriction but also to airway inflammation and remodeling, as implied by experimental and clinical evidence. We here summarize the current understanding of the actions/signaling of GCs in asthma, and specifically, GC receptor (GR) “site-specific phosphorylation” and its role in regulating GC actions. We also review some common pitfalls associated with studies investigating GCI and the inflammatory mediators linked to asthma severity. Finally, we discuss and contrast potential molecular mechanisms underlying the impairment of GC actions in immune cells versus non-immune cells such as ASM cells.
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影响因子：
5.8
作者：
Seidel P;Alkhouri H;Lalor DJ;Burgess JK;Armour CL;Hughes JM
通讯作者：
Hughes JM
DOI：
10.1164/ajrccm.154.6.8970374
发表时间：
1996-12-01
影响因子：
24.7
作者：
Berkman, N;Krishnan, VL;Chung, KF
通讯作者：
Chung, KF
DOI：
10.1165/ajrcmb.26.4.4681
发表时间：
2002-04-01
影响因子：
6.4
作者：
Ammit, AJ;Lazaar, AL;Panettieri, RA
通讯作者：
Panettieri, RA
糖皮质激素受体激活蛋白1在类固醇哮喘中的相互作用。
影响因子：
15.3
作者：
Adcock, Ian M.;Lane, Stephen J.;Brown, Carolanne R.;Lee, Tak H.;Barnes, Peter J.
通讯作者：
Barnes, Peter J.
DOI：
10.1164/ajrccm/147.2.405
发表时间：
1993-02-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
CARROLL, N;ELLIOT, J;JAMES, A
通讯作者：
JAMES, A