A low dose of Mycoplasma pneumoniae infection enhances an established allergic inflammation in mice: the role of the prostaglandin E2 pathway.
A low dose of Mycoplasma pneumoniae infection enhances an established allergic inflammation in mice: the role of the prostaglandin E2 pathway.
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DOI：
10.1111/j.1365-2222.2009.03309.x
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Chu HW
中科院分区：
文献类型：
--
作者：
Wu Q;Martin RJ;LaFasto S;Chu HW
超过40%的慢性稳定型哮喘患者有呼吸道肺炎支原体（MP）感染的证据，通过聚合酶链反应（PCR）检测，但不是通过血清学和培养，表明低水平的MP参与慢性哮喘。然而，这种低水平的MP感染在调节过敏性炎症中的作用仍然未知。为了确定低水平Mp感染在具有已建立的气道过敏性炎症的小鼠中对过敏反应如嗜酸性粒细胞增多症和趋化因子eotaxin-2的影响，以及潜在的机制（即，前列腺素E2 [PGE 2]途径），因为在过敏原激发前吸入PGE 2抑制了人气道中的嗜酸性粒细胞浸润。采用卵清蛋白（OVA）诱导的过敏性哮喘BALB/c小鼠模型，随后使用低剂量或高剂量MP，以评估IL-4表达，BAL嗜酸性粒细胞，嗜酸性粒细胞趋化因子-2和PGE 2水平，以及微粒体前列腺素E合成酶-1（mPGES-1）的肺mRNA水平。培养来自幼稚BALB/c小鼠的原代肺泡巨噬细胞（pAM）以确定MP诱导的PGE 2或外源性PGE 2是否下调IL-4/IL-13诱导的嗜酸性粒细胞活化趋化因子-2。低剂量MP在过敏小鼠中显著增强IL-4和Eotaxin-2，并适度促进肺嗜酸性粒细胞增多，而高剂量MP显著降低肺嗜酸性粒细胞增多，并倾向于降低IL-4和Eotaxin-2。此外，在OVA初治和过敏小鼠中，肺mPGES-1 mRNA和BAL PGE 2水平在高剂量MP感染的小鼠中升高，但在低剂量MP感染的小鼠中未升高。在pAMs中，IL-4/IL-13显著增加了嗜酸性粒细胞趋化因子-2，其被Mp感染伴随剂量依赖性PGE 2诱导而减少。外源性PGE 2以剂量依赖性方式抑制IL-4/IL-13诱导的eotaxin-2。这项研究强调了一个新的概念，即肺中不同的细菌负荷如何改变已建立的过敏性气道炎症，从而与过敏原相互作用，进一步诱导Th 2应答。也就是说：与高水平Mp不同，低水平Mp不能有效诱导PGE 2下调过敏反应（例如，嗜酸性粒细胞趋化因子-2），从而维持或甚至恶化哮喘气道中的过敏性炎症。
Over 40% of chronic stable asthma patients have evidence of respiratory Mycoplasma pneumoniae (Mp) infection as detected by polymerase chain reaction (PCR), but not by serology and culture, suggesting a low-level Mp involved in chronic asthma. However, the role of such a low-level Mp infection in regulation of allergic inflammation remains unknown. To determine the impact of a low-level Mp infection in mice with established airway allergic inflammation on allergic responses such as eosinophilia and chemokine eotaxin-2, and the underlying mechanisms (i.e., prostaglandin E2 [PGE2] pathway) since PGE2 inhalation before allergen challenge suppressed eosinophil infiltration in human airways. BALB/c mouse models of ovalbumin (OVA)-induced allergic asthma with an ensuing low-dose or high-dose Mp were used to assess IL-4 expression, BAL eosinophil, eotaxin-2 and PGE2 levels, and lung mRNA levels of microsomal prostaglandin E synthase-1 (mPGES-1). Primary alveolar macrophages (pAMs) from naïve BALB/c mice were cultured to determine if Mp-induced PGE2 or exogenous PGE2 down-regulates IL-4/IL-13-induced eotaxin-2. Low-dose Mp in allergic mice significantly enhanced IL-4 and eotaxin-2, and moderately promoted lung eosinophilia, whereas high-dose Mp significantly reduced lung eosinophilia and tended to decrease IL-4 and eotaxin-2. Moreover, in both OVA-naïve and allergic mice, lung mPGES-1 mRNA and BAL PGE2 levels were elevated in mice infected with high-dose, but not low-dose Mp. In pAMs, IL-4/IL-13 significantly increased eotaxin-2, which was reduced by Mp infection accompanied by dose-dependent PGE2 induction. Exogenous PGE2 inhibited IL-4/IL-13-induced eotaxin-2 in a dose-dependent manner. This study highlights a novel concept on how differing bacterial loads in the lung modify the established allergic airway inflammation, and thus interact with an allergen to further induce Th2 responses. That is: Unlike high-level Mp, low-level Mp fails to effectively induce PGE2 to down-regulate allergic responses (e.g., eotaxin-2), thus maintaining or even worsening allergic inflammation in asthmatic airways.
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影响因子：
4.4
作者：
Martin, JG;Suzuki, M;Powell, WS
通讯作者：
Powell, WS
DOI：
10.1164/ajrccm.160.2.9809130
发表时间：
1999-08-01
影响因子：
24.7
作者：
Gauvreau, GM;Watson, RM;O'Byrne, PM
通讯作者：
O'Byrne, PM
影响因子：
4.8
作者：
Kitaura, M;Suzuki, N;Yoshie, O
通讯作者：
Yoshie, O
DOI：
10.1006/bbrc.1993.2599
发表时间：
1993-12-30
影响因子：
3.1
作者：
GRIFFITHSJOHNSON, DA;COLLINS, PD;WILLIAMS, TJ
通讯作者：
WILLIAMS, TJ
影响因子：
4.4
作者：
Chu, Hong Wei;Thaikoottathil, Jyoti;Martin, Richard J.
通讯作者：
Martin, Richard J.