scholarly journals The Role of Protein Kinase mTOR in Th2 Polarization of the Immune Response in Bronchial Asthma in Сhildren

2015 ◽  
Vol 0 (7.67) ◽  
pp. 6-11
Author(s):  
O.P. Volosovets ◽  
S.P. Kryvopustov ◽  
O.V. Pavlyk
Keyword(s):  
Immune Response ◽  
Protein Kinase ◽  
Bronchial Asthma ◽  
Th2 Polarization

scholarly journals The Protein Kinase Receptor Modulates the Innate Immune Response against Tacaribe Virus

2021 ◽  
Author(s):  
Hector Moreno ◽  
Stefan Kunz
Keyword(s):  
Immune Response ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Protein Expression ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Protein Synthesis Inhibition ◽  
Highly Pathogenic ◽  
Tacaribe Virus

The New World (NW) mammarenavirus group includes several zoonotic highly pathogenic viruses, such as Junin (JUNV) or Machupo (MACV). Contrary to Old World mammarenavirus, these viruses are not able to completely suppress the innate immune response, and trigger a robust interferon (IFN)-I response via retinoic acid-inducible gene I (RIG-I). Nevertheless, pathogenic NW mammarenaviruses trigger a weaker IFN response than their non-pathogenic relatives do. RIG-I activation leads to upregulation of a plethora of IFN-stimulated genes (ISGs), which exert a characteristic antiviral effect either as lone effectors, or resulting from the combination with other ISGs or cellular factors. The dsRNA sensor-protein kinase receptor (PKR) is an ISG that plays a pivotal role in the control of the mammarenavirus infection. In addition to its well-known protein synthesis inhibition, PKR further modulates the overall IFN-I response against different viruses, including mammarenaviruses. For this study, we employed Tacaribe virus (TCRV), the closest relative of the human pathogenic JUNV. Our findings indicate that PKR does not only increase IFN-I expression against TCRV infection, but also affects the kinetic expression and the extent of induction of Mx1 and ISG15 at both levels, mRNA and protein expression. Moreover, TCRV fails to prevent the effect of PKR on viral protein translation and its viral titer is inhibited when PKR is pre-stimulated via IFN-I. Here, we provide first evidence of the specific immunomodulatory role of PKR over selected ISGs, altering the dynamic of the innate immune response course against TCRV. IMPORTANCE: The mechanisms for innate immune evasion are key for emergence and adaptation of human pathogenic arenaviruses, and highly pathogenic mammarenaviruses such as JUNV or MACV trigger a weaker IFN response than non-pathogenic mammarenaviruses. Within the innate immune response context, PKR plays an important role in sensing and restricting the infection of TCRV virus. Although the mechanism of PKR for protein synthesis inhibition is well described, its immunomodulatory role is less understood. In this study, we found that TCRV protein expression and viral propagation are inhibited from early times after infection, and when externally activated, PKR inhibits TCRV viral progeny production. Our present findings further characterize the innate immune response in absence of PKR, unveiling the role of PKR in defining the ISG profile after viral infection.

scholarly journals Chitotriosidase: a marker and modulator of lung disease

2020 ◽  
Vol 29 (156) ◽  
pp. 190143 ◽  
Author(s):  
De Chang ◽  
Lokesh Sharma ◽  
Charles S. Dela Cruz
Keyword(s):  
Immune Response ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Bronchial Asthma ◽  
Tissue Damage ◽  
Lung Diseases ◽  
Molecular Pathogenesis ◽  
Activated Macrophages ◽  
Pulmonary Infections

Chitotriosidase (CHIT1) is a highly conserved and regulated chitinase secreted by activated macrophages; it is a member of the 18-glycosylase family (GH18). CHIT1 is the most prominent chitinase in humans, can cleave chitin and participates in the body's immune response and is associated with inflammation, infection, tissue damage and remodelling processes. Recently, CHIT1 has been reported to be involved in the molecular pathogenesis of pulmonary fibrosis, bronchial asthma, COPD and pulmonary infections, shedding new light on the role of these proteins in lung pathophysiology. The potential roles of CHIT1 in lung diseases are reviewed in this article.

scholarly journals The Protein Kinase Receptor Modulates the Innate Immune Response against Tacaribe Virus

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1313
Author(s):  
Hector Moreno ◽  
Stefan Kunz
Keyword(s):  
Immune Response ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Protein Synthesis Inhibition ◽  
Highly Pathogenic ◽  
Synthesis Inhibition ◽  
Tacaribe Virus

The New World (NW) mammarenavirus group includes several zoonotic highly pathogenic viruses, such as Junin (JUNV) or Machupo (MACV). Contrary to the Old World mammarenavirus group, these viruses are not able to completely suppress the innate immune response and trigger a robust interferon (IFN)-I response via retinoic acid-inducible gene I (RIG-I). Nevertheless, pathogenic NW mammarenaviruses trigger a weaker IFN response than their nonpathogenic relatives do. RIG-I activation leads to upregulation of a plethora of IFN-stimulated genes (ISGs), which exert a characteristic antiviral effect either as lone effectors, or resulting from the combination with other ISGs or cellular factors. The dsRNA sensor protein kinase receptor (PKR) is an ISG that plays a pivotal role in the control of the mammarenavirus infection. In addition to its well-known protein synthesis inhibition, PKR further modulates the overall IFN-I response against different viruses, including mammarenaviruses. For this study, we employed Tacaribe virus (TCRV), the closest relative of the human pathogenic JUNV. Our findings indicate that PKR does not only increase IFN-I expression against TCRV infection, but also affects the kinetic expression and the extent of induction of Mx1 and ISG15 at both levels, mRNA and protein expression. Moreover, TCRV fails to suppress the effect of activated PKR, resulting in the inhibition of a viral titer. Here, we provide original evidence of the specific immunomodulatory role of PKR over selected ISGs, altering the dynamic of the innate immune response course against TCRV. The mechanisms for innate immune evasion are key for the emergence and adaptation of human pathogenic arenaviruses, and highly pathogenic mammarenaviruses, such as JUNV or MACV, trigger a weaker IFN response than nonpathogenic mammarenaviruses. Within the innate immune response context, PKR plays an important role in sensing and restricting the infection of TCRV virus. Although the mechanism of PKR for protein synthesis inhibition is well described, its immunomodulatory role is less understood. Our present findings further characterize the innate immune response in the absence of PKR, unveiling the role of PKR in defining the ISG profile after viral infection. Moreover, TCRV fails to suppress activated PKR, resulting in viral progeny production inhibition.

scholarly journals RNA-activated protein kinase differentially modulates innate immune response mediated by supraphysiological concentrations of thyroid hormone

2020 ◽  
Vol 26 (8) ◽  
pp. 746-758
Author(s):  
Mohammad Ishaq ◽  
Ven Natarajan
Keyword(s):  
Immune Response ◽  
Thyroid Hormone ◽  
Protein Kinase ◽  
Innate Immune Response ◽  
Phosphatidyl Inositol ◽  
Nuclear Hormone Receptor ◽  
Innate Immune ◽  
Receptor Ligands ◽  
Polycytidylic Acid

Nuclear hormone receptor ligands are known to modulate innate immunity by dampening the immune response induced by pathogens. Here, we report that unlike other ligands, 3,3′,5-triiodo-l-thyronine (T3) induced the type 1 IFN response and expression of IFN-stimulated genes (ISGs). T3 action was found to be significantly amplified at supraphysiological concentrations (SPC) and in combination with double-stranded RNA mimic polyinosinic–polycytidylic acid. Induction by T3 was due to non-genomic mechanisms involving integrin binding, calcium mobilization, and phosphatidyl-inositol 3-kinase–AKT pathways, but was independent of TLR3, RIG-I, and IFN-β1 pathways. Whereas siRNA-induced knockdown of RNA-activated protein kinase (PKR) was found to abrogate the T3-induced expression of select ISGs, expression of other T3-induced ISGs was strongly induced by PKR knockdown, indicating the differential role of PKR in modulating T3 action. Together, we describe a novel role of T3 in modulating the innate immune response and identify the importance of PKR in regulating T3-induced immune activation. These findings have important implications in the basic understanding of the mechanisms of T3 function at SPCs and crosstalk involved in the thyroid hormone function and the innate immune response.

scholarly journals The Role of CDK5 in Tumours and Tumour Microenvironments

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 101
Author(s):  
Phuong Anh Do ◽  
Chang Hoon Lee
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Cancer Treatment ◽  
Tumour Progression ◽  
Cancer Development ◽  
Cyclin Dependent Kinase ◽  
Neuronal Function ◽  
Cyclin Dependent Kinase 5

Cyclin-dependent kinase 5 (CDK5), which belongs to the protein kinase family, regulates neuronal function but is also associated with cancer development and has been proposed as a target for cancer treatment. Indeed, CDK5 has roles in cell proliferation, apoptosis, angiogenesis, inflammation, and immune response. Aberrant CDK5 activation triggers tumour progression in numerous types of cancer. In this review, we summarise the role of CDK5 in cancer and neurons and CDK5 inhibitors. We expect that our review helps researchers to develop CDK5 inhibitors as treatments for refractory cancer.

scholarly journals Mitochondrial dsRNAs activate PKR and TLR3 to promote chondrocyte degeneration in osteoarthritis

2020 ◽  
Author(s):  
Sujin Kim ◽  
Keonyong Lee ◽  
Yong Seok Choi ◽  
Jayoung Ku ◽  
Yun Jong Lee ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Kinase ◽  
Inflammatory Cytokines ◽  
Degenerative Diseases ◽  
Toll Like Receptor ◽  
Protein Kinase R ◽  
Molecular Identity ◽  
Synovial Fluids ◽  
Elevated Expression

ABSTRACTProtein kinase R (PKR) is an immune response protein that becomes activated by long double-stranded RNAs (dsRNAs). Several studies reported the misactivation of PKR in patients of degenerative diseases including primary osteoarthritis (OA). However, the molecular identity of PKR-activating dsRNAs remains unknown. Here, we investigate the role of mitochondrial dsRNAs (mt-dsRNAs) in the development of OA. We find that in response to OA-mimicking stressors, cytosolic efflux of mt-dsRNAs is increased, leading to PKR activation and subsequent induction of inflammatory cytokines and apoptosis. Moreover, mt-dsRNAs are exported to the extracellular space where they activate toll-like receptor 3. Elevated expression of mt-dsRNAs in the synovial fluids of OA patients further supports our data. Lastly, we show that autophagy protects chondrocytes from mitochondrial dysfunction partly by removing cytosolic mt-dsRNAs. Together, these findings establish the PKR-mt-dsRNA as a critical regulatory axis in OA development and suggest mt-dsRNAs as a potential target in fighting OA.

scholarly journals Blockade of Wnt/β-Catenin Pathway Aggravated Silica-Induced Lung Inflammation through Tregs Regulation on Th Immune Responses

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Wujing Dai ◽  
Fangwei Liu ◽  
Chao Li ◽  
Yiping Lu ◽  
Xiaowei Lu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Lung Inflammation ◽  
Intratracheal Instillation ◽  
Mice Model ◽  
Th2 Response ◽  
Th17 Response ◽  
Th2 Polarization

CD4+T cells play an important role in regulating silica-induced inflammation and fibrosis. Recent studies showed that Wnt/β-catenin pathway could modulate the function and the differentiation of CD4+T cells. Therefore, Wnt/β-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/β-catenin pathway, we used lentivirus expressingβ-catenin shRNA to block the Wnt/β-catenin pathway by intratracheal instillation to the mice model of silicosis. Treatment of lentivirus could significantly aggravate the silica-induced lung inflammation and attenuated the fibrosis at the late stage. By analyzing CD4+T cells, we found that blockade of Wnt/β-catenin pathway suppressed regulatory T cells (Tregs). Reciprocally, enhanced Th17 response was responsible for the further accumulation of neutrophils and production of proinflammatory cytokines. In addition, blockade of Wnt/β-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/β-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/β-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis.

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