Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection
Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection
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DOI：
10.1038/s41598-019-43417-x
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发表时间：
2019-05-07
影响因子：
4.6
通讯作者：
Obonyo, Marygorret
中科院分区：
文献类型：
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作者：
Mejias-Luque, Raquel;Lozano-Pope, Ivonne;Obonyo, Marygorret
幽门螺杆菌感染诱导了一系列促炎信号通路，导致胃炎症和癌变。其中，NF-κ B信号传导在胃上皮感染和恶性转化过程中发挥着关键作用。然而，通过NF-κ B B传递信号的衔接分子髓样分化初级反应88（MyD 88）的缺乏导致H后胃病理学的加速发展。猫感染，但导致这种表型的机制仍然难以捉摸。非经典NF-κ B信号转导被证明可加重H。幽门螺杆菌诱导的胃炎症，通过激活胃光敏素β受体（LT β R）。在本研究中，我们探讨了在MyD 88缺陷（Myd 88（-/-））小鼠中观察到的恶化的病理学是否与非典型NF-κ B B的异常激活相关。我们的结果表明，在MyD 88缺失的情况下，H.猫感染增强了非典型NF-κ B B的活化，这与Cxcl 9和Icam 1基因表达的增加以及CD 3（+）淋巴细胞募集有关。此外，与野生型（WT）小鼠相比，Myd 88（-/-）中信号转导子和转录激活子3（STAT 3）信号传导的激活更高，表明MyD 88缺陷和STAT 3响应于H.猫感染因此，MyD 88缺陷导致由螺杆菌通过激活非典型NF-κ B诱导的胃病理学加速和加重。
Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis. Among those, NF-kappa B signaling plays a pivotal role during infection and malignant transformation of the gastric epithelium. However, deficiency of the adaptor molecule myeloid differentiation primary response 88 (MyD88), which signals through NF-kappa B, led to an accelerated development of gastric pathology upon H. felis infection, but the mechanisms leading to this phenotype remained elusive. Non-canonical NF-kappa B signaling was shown to aggravate H. pylori-induced gastric inflammation via activation of the lymphotoxin beta receptor (LT beta R). In the present study, we explored whether the exacerbated pathology observed in MyD88-deficient (Myd88(-/-)) mice was associated with aberrant activation of non-canonical NF-kappa B. Our results indicate that, in the absence of MyD88, H. felis infection enhances the activation of non-canonical NF-kappa B that is associated with increase in Cxcl9 and Icam1 gene expression and CD3(+) lymphocyte recruitment. In addition, activation of signal transducer and activator of transcription 3 (STAT3) signaling was higher in Myd88(-/-) compared to wild type (WT) mice, indicating a link between MyD88 deficiency and STAT3 activation in response to H. felis infection. Thereby, MyD88 deficiency results in accelerated and aggravated gastric pathology induced by Helicobacter through activation of non-canonical NF-kappa B.