Downregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop

Liu, Zhiyong; Qin, Qiang; Wu, Cheng Hsien; Li, Hui; Shou, Jianan; Yang, Yuting; Gu, Meidi; Ma, Chunmei; Lin, Wenlong; Zou, Yan; Zhang, Yuanyuan; Ma, Feng; Sun, Jihong; Wang, Xiaojian

doi:10.1038/s41467-018-05176-7

Cited by 24 publications

(22 citation statements)

References 38 publications

(53 reference statements)

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“…Thioglycolate-elicited mouse primary peritoneal macrophages were prepared from female C57BL/6J mice (6-8 weeks of age) as described previously (Jiang et al, 2017). Adherent cells were used as mouse primary peritoneal macrophages after 2 h. Immortalized bone marrow-derived macrophages (iBMDMs) were maintained in RPMI-1640 medium supplemented with 10% FBS and 20 ng/ml macrophage colony-stimulating factor (PeproTech, Rocky Hill, NJ, USA) (Liu Z. et al, 2018). All cells were cultured at 37°C in a humidified incubator containing 5% CO2.…”

Section: Cell Culturementioning

confidence: 99%

Xuebijing Injection Alleviates Pam3CSK4-Induced Inflammatory Response and Protects Mice From Sepsis Caused by Methicillin-Resistant Staphylococcus aureus

Qian

Miao

et al. 2020

Front. Pharmacol.

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A leading cause of death worldwide is sepsis that develops as a dysregulated immune response to infection. Serious infection caused by methicillin-resistant Staphylococcus aureus (MRSA) increases the difficulty of treatment in septic patients. Host-directed therapy (HDT) is an emerging approach to bacterial infections. Xuebijing injection (XBJ), a commercialized injectable prescription from traditional Chinese medicine, has been used as adjuvant therapy for sepsis with a history of 15 years. Whether it plays a protective role in severe infection caused by antibiotic-resistant bacteria is still unknown. In this study, XBJ significantly improved the survival of MRSA-induced sepsis mice. In MRSA-infected mouse model, XBJ down-regulated the expression of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-a, MCP-1, MIP-2, and IL-10 in sera. Besides that, it decreased the bacterial load in spleens, livers, and alleviated tissue damage of lung, liver, and kidney. The combination of XBJ with vancomycin or dexamethasone exhibited a better down-regulatory role of the inflammatory response. Then, the protective mechanism of XBJ was further investigated. XBJ inhibited heatkilled MRSA-induced IL-6 and TNF-a production in mouse macrophages. XBJ also decreased Pam3CSK4 (a synthetic tripalmitoylated lipopeptide mimicking bacterial lipoproteins)stimulated expression of IL-6, TNF-a, IL-1b, IL-12, etc. in mouse macrophages. Furthermore, XBJ down-regulated the activation of NF-kB, MAPK, and PI3K/Akt pathways in Pam3CSK4-stimulated mouse macrophages. In conclusion, our findings demonstrated that XBJ played a protective role in MRSA-challenged mice and down-regulated the inflammatory response and the activation of signaling pathways initiated by Pam3CSK4. It enlarged the clinical application of XBJ in the treatment of severe bacterial infection, e.g. caused by MRSA.

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Section: Cell Culturementioning

confidence: 99%

Xuebijing Injection Alleviates Pam3CSK4-Induced Inflammatory Response and Protects Mice From Sepsis Caused by Methicillin-Resistant Staphylococcus aureus

Qian

Miao

et al. 2020

Front. Pharmacol.

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“…Mechanistically, NDR1 increases the translation of the transcription factor STAT1 by directly linking to the intergenic region of miR146a. These new molecular findings show that IFN-dependent antiviral immune response, residing on NDR1 is an important molecular mechanism of viral infections control (Liu et al, 2018).…”

Section: Introductionmentioning

confidence: 81%

Syncitial virus respiratory infections in children – immunological aspects

Munteanu¹,

Surcel²,

Constantin³

et al. 2019

Rev. Biol. Biomed. Sci.

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Out of all respiratory viral infections, those with human respiratory syncytial virus (HRSV) are the most frequent registered worldwide being responsible for bronchiolitis, pneumonia, and asthma in all age groups, especially in children. As children have an immature immune system, severe HRSV infection can lead to death. In this paper we will revise the most recent findings regarding the immune response in the HRSV infection focusing on children. Extensive studies indicate that viral and host factors modulate the severity of infection. The viral infection first triggers a strong innate immune response followed by a further adaptive immune antiviral response. Although HRSV infection is common, there is still no efficient therapy available. The hurdles in obtaining an efficient therapy reside in several issues: the immaturity of the immune system of infants and young children, the differences in the virulence potential of the viral strains that induce a different cytokine/chemokine host response, with the involvement of multiple molecular, still unknown pathways. Identification of antiviral immune mechanisms and the comprehensive characterization of virus-specific immune responses using new cellular and animal models would help to define the crosstalk between viral and host factors that would modulate the severity of infection. Moreover identifying the molecular mechanisms of acute airway disease would shed light also on associated long-term consequences like developing asthma in the adulthood. As HRSV is globally circulating for more than 60 years, an effective therapy remains a public health priority.

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“…STAT1 translation subsequently increases the production of type I IFN, pro-inflammatory cytokines and interferon-stimulated genes (ISGs) for the antiviral immune response. These findings revealed that NDR1 positively regulates type I and type II IFN pathways and enhances antiviral immune response (6). Glycogen synthase kinase 3β (GSK3β) and STAT1 are important participants in the antiviral immune response.…”

Section: Ndr Regulates Pattern Recognition Receptor-mediated Innate Imentioning

confidence: 95%

“…NDR1 (Stk38) mainly distributes in the nuclei. NDR2, on the other hand, is defined as a cytoplasmic kinase (4)(5)(6)(7). In addition to a central kinase catalytic domain, NDR1 and NDR2 each has a conserved N-terminal regulatory domain (NTR) and a C-terminal hydrophobic motif (8).…”

Section: Introductionmentioning

confidence: 99%

The Emerging Roles of NDR1/2 in Infection and Inflammation

Ong

et al. 2020

Front. Immunol.

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The nuclear Dbf2-related (NDR) kinases NDR1 and NDR2 belong to the NDR/LATS (large tumor suppressor) subfamily in the Hippo signaling pathway. They are highly conserved from yeast to humans. It is well-known that NDR1/2 control important cellular processes, such as morphological changes, centrosome duplication, cell proliferation, and apoptosis. Recent studies revealed that NDR1/2 also play important roles in the regulation of infection and inflammation. In this review, we summarized the roles of NDR1/2 in the modulation of inflammation induced by cytokines and innate immune response against the infection of bacteria and viruses, emphasizing on how NDR1/2 regulate signaling transduction through Hippo pathway-dependent and-independent manners.

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Downregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop

Cited by 24 publications

References 38 publications

Xuebijing Injection Alleviates Pam3CSK4-Induced Inflammatory Response and Protects Mice From Sepsis Caused by Methicillin-Resistant Staphylococcus aureus

Xuebijing Injection Alleviates Pam3CSK4-Induced Inflammatory Response and Protects Mice From Sepsis Caused by Methicillin-Resistant Staphylococcus aureus

Syncitial virus respiratory infections in children – immunological aspects

The Emerging Roles of NDR1/2 in Infection and Inflammation

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