SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells.
SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells.
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DOI：
10.4049/jimmunol.1100573
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Kraft M
中科院分区：
文献类型：
--
作者：
Wang Y;Zhu Z;Church TD;Lugogo NL;Que LG;Francisco D;Ingram JL;Huggins M;Beaver DM;Wright JR;Kraft M
哮喘是一种慢性炎症性疾病，其中气道上皮细胞是抵抗气道暴露于感染因子的第一道防线。Src同源蛋白(SHP)-1是一种蛋白酪氨酸磷酸酶，是对哮喘和宿主防御发展至关重要的信号通路的负调节因子。我们假设SHP-1功能在哮喘中存在缺陷，导致肺炎支原体（一种已知会加剧哮喘的病原体）诱导的炎症反应增加。肺炎支原体显著激活非哮喘患者气道上皮细胞中的SHP-1，但哮喘患者的细胞中没有。在哮喘气道上皮细胞中，与非哮喘细胞相比，肺炎支原体诱导了显著的PI3K/Akt磷酸化、NF-κB激活和IL-8的产生，这些被SHP-1过表达逆转。相反，在肺炎支原体感染的非哮喘细胞中，SHP-1敲低显著增加IL-8的产生以及PI3K/Akt和NF-κB的激活，但没有加剧哮喘细胞中已经激活的这三个参数。因此，SHP-1通过抑制PI3K/Akt和NF-κB活性，在非哮喘气道上皮细胞中抑制肺炎支原体诱导的IL-8产生中发挥关键作用，但在哮喘中存在缺陷，导致感染的炎症反应增强。
Asthma is a chronic inflammatory disease in which airway epithelial cells are the first line of defense against exposure of the airway to infectious agents. Src homology protein (SHP)-1, a protein tyrosine phosphatase, is a negative regulator of signaling pathways that are critical to the development of asthma and host defense. We hypothesize that SHP-1 function is defective in asthma, contributing to the increased inflammatory response induced by Mycoplasma pneumoniae, a pathogen known to exacerbate asthma. M. pneumoniae significantly activated SHP-1 in airway epithelial cells collected from nonasthmatic subjects by bronchoscopy with airway brushing but not in cells from asthmatic subjects. In asthmatic airway epithelial cells, M. pneumoniae induced significant PI3K/Akt phosphorylation, NF-κB activation, and IL-8 production compared with nonasthmatic cells, which were reversed by SHP-1 overexpression. Conversely, SHP-1 knockdown significantly increased IL-8 production and PI3K/Akt and NF-κB activation in the setting of M. pneumoniae infection in nonasthmatic cells, but it did not exacerbate these three parameters already activated in asthmatic cells. Thus, SHP-1 plays a critical role in abrogating M. pneumoniae-induced IL-8 production in non-asthmatic airway epithelial cells through inhibition of PI3K/Akt and NF-κB activity, but it is defective in asthma, resulting in an enhanced inflammatory response to infection.
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影响因子：
4.4
作者：
Kashiwada, M;Giallourakis, CC;Rothman, PB
通讯作者：
Rothman, PB
DOI：
10.1164/ajrccm/145.3.669
发表时间：
1992-03-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
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通讯作者：
HOLGATE, ST
影响因子：
4.8
作者：
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通讯作者：
Mills, GB
影响因子：
32.4
作者：
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通讯作者：
GOODNOW, CC
影响因子：
4.3
作者：
Khaled, AR;Butfiloski, EJ;Schiffenbauer, J
通讯作者：
Schiffenbauer, J