scholarly journals Higher expression of monocyte chemotactic protein 1 in mild COVID-19 patients may be correlated with the inhibition of IFN signaling

2020 ◽  
Author(s):  
Xueyan Xi ◽  
Yang Guo ◽  
Min Zhu ◽  
Yuhui Wei ◽  
Gang Li ◽  
...  

Abstract Background: The level of chemokines was markedly elevated in severe COVID-19 patients. But the role of chemokines in mild COVID-19 has not yet been established. However, most of the COVID-19 patients in Shiyan City, China, had mild cases. The purpose of this study is to evaluate the level of chemokines in mild COVID-19 patients and explore the correlation between chemokines and host immune response.Methods: In this study, the level of chemokines in the serum for COVID-19 patients in Shiyan City was detected by ELISA. The expression of chemokine receptors and other signal molecules was measured by real-time PCR.Results: We first demonstrated that COVID-19 patients are characterized by higher level of chemokines. Meanwhile, monocyte chemotactic protein 1 (MCP-1) has also shown higher expression in patients with mild cases of COVID-19. The receptor of MCP-1, CCR2, was also found to be expressed at higher level in the same mild COVID-19 patients. Finally, we found the downregulation of interferon regulatory factor 3 (IRF3) was significantly negative correlated with the concentration of MCP-1 in mild COVID-19 patients.Conclusion: Higher expression of MCP-1 in mild COVID-19 patients may be correlated with the inhibition of IFN signaling. The finding adds our understanding to the immune-pathologic mechanisms of SARS-CoV-2 infection, and provides potential therapeutic targets and strategies.

2020 ◽  
Author(s):  
Xueyan Xi ◽  
Yang Guo ◽  
Min Zhu ◽  
Yuhui Wei ◽  
Gang Li ◽  
...  

Abstract Background: The level of chemokine was markedly elevated in severe COVID-19 patients. But the role of chemokine in mild COVID-19 has not yet been established. However, most of the COVID-19 patients in Shiyan City, China, had mild cases. The purpose of this study is to evaluate the level of chemokine in mild COVID-19 patients and to explore the correlation between chemokine and host immune response.Methods: In this study, the level of chemokine in the serum for COVID-19 patients in Shiyan City was detected by ELISA. The expression of chemokine receptor and other signal molecular was detected by real-time PCR. Results: We first demonstrated that COVID-19 patients are characterized by higher levels of chemokine. Meanwhile, monocyte chemotactic protein 1 (MCP-1) has shown higher expression in patients with mild cases of COVID-19. The receptor of MCP-1, CCR2 was also found to be expressed at higher levels in the same mild COVID-19 patients. Finally, the higher expression of MCP-1 in mild COVID-19 patients is correlated with the inhibition of IFN signaling. Conclusion: These findings add to our understanding of the immune-pathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies. MCP-1 may be an effective indicator in mild patients, and early use of interferon has a good antiviral therapeutic effect.


2020 ◽  
Author(s):  
xueyan xi ◽  
Yang Guo ◽  
Min Zhu ◽  
Yuhui Wei ◽  
Gang Li ◽  
...  

Abstract Background: The level of chemokine was markedly elevated in severe COVID-19 patients. But the role of chemokine in mild COVID-19 patients has not yet established. However, most of the COVID-19 patients in Shiyan City, China had mild cases. Methods: In this study, the level of chemokine in the serum for COVID-19 patients in Shiyan City was detected by ELISA. The expression of receptor of chemokine and other signal molecular was detected by real-time PCR. Results: We first demonstrated that COVID-19 patients are characterized by higher levels of chemokine. In particular, monocyte chemotactic protein 1 (MCP-1) has shown higher expression in patients with mild cases of COVID-19. The receptor of MCP-1, CCR2 was then found higher expression in the same mild COVID-19 patients. Finally, the higher expression of MCP-1 in mild COVID-19 patients is correlated with the inhibition of IFN signaling. Conclusion: These findings add to our understanding of the immune-pathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies. MCP-1 may be an effective indicator in mild patients, and early use of interferon has a good antiviral therapeutic effect.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yamaguchi R ◽  
◽  
Sakamoto A ◽  
Haraguchi M ◽  
Narahara S ◽  
...  

The pathogenesis of pulmonary fibrosis remains unknown. However, bacterial infections in patients with idiopathic pulmonary fibrosis are a serious complication that exacerbate the disease. Serum levels of Surfactant Protein D (SPD) are known to be elevated in patients with pulmonary fibrosis, but the role of SPD in pulmonary fibrosis complicated with bacterial infection is unknown. Lipopolysaccharide upregulates Interleukin (IL)-12p40 expression and IL-12p40 promotes Interferon Gamma (IFNγ) production to induce the T helper cell 1 (Th1) immune response via Signal Transducers and Activators of Transcription 4 (STAT4) signaling. A lack of IFNγ shifts the immune response from Th1 to Th2. IL-4 is a profibrotic Th2 cytokine that activates fibroblasts. Granulocyte-macrophage colony-stimulating factor induced by IL-1 and TNFα during the Th1 immune response upregulates Signal Regulatory Protein α (SIRPα) expression. Interferon Regulatory Factor 1 (IRF1) functions as the promoter activator of IL-12p40 after stimulation with LPS. SPD is a ligand for SIRPα, and SPD/SIRPα ligation activates the Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Related Kinase (ERK) signal cascade; ERK downregulates Interferon Regulatory Factor 1 (IRF1) expression. Consequently, the SPD/SIRPα signaling pathway decreases IL-12p40 production in human macrophages after exposure to LPS. IL-12p40 is a key immunoregulatory factor in bacterial infection that promotes production of IFNγ by T lymphocytes. Pulmonary fibroblasts are activated by IL-4/IL-4R ligation. IFNγ induces IRF1 via STAT1 signaling, and IRF1 acts as the promoter repressor of IL-4 to attenuate its production. IFNγ also inhibits IL-4R expression. A reduction in IFNγ induced by IL-12p40 deficiency via the SPD/SIRPα signaling pathway enhances IL-4 and IL-4R expression to augment the activity of fibroblasts. This finding indicates that pulmonary fibrosis is exacerbated by SPD/SIRPα signaling during bacterial infection.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xueyan Xi ◽  
Yang Guo ◽  
Min Zhu ◽  
Yuhui Wei ◽  
Gang Li ◽  
...  

Abstract Background Chemokine levels in severe coronavirus disease 2019 (COVID-19) patients have been shown to be markedly elevated. But the role of chemokines in mild COVID-19 has not yet been established. According to the epidemiological statistics, most of the COVID-19 cases in Shiyan City, China, have been mild. The purpose of this study was to evaluate the level of chemokines in mild COVID-19 patients and explore the correlation between chemokines and host immune response. Methods In this study, we used an enzyme-linked immunosorbent assay to detect serum levels of chemokines in COVID-19 patients in Shiyan City. Expression of chemokine receptors and of other signaling molecules was measured by real-time polymerase chain reaction. Results We first demonstrated that COVID-19 patients, both sever and mild cases, are characterized by higher level of chemokines. Specifically, monocyte chemotactic protein 1 (MCP-1) is expressed at higher levels both in severe and mild cases of COVID-19. The receptor of MCP-1, C-C chemokine receptor type 2, was expressed at higher levels in mild COVID-19 patients. Finally, we observed a significant negative correlation between expression levels of interferon (IFN) regulatory factor 3 (IRF3) and serum levels of MCP-1 in mild COVID-19 patients. Conclusion Higher expression of MCP-1 in mild COVID-19 patients might be correlated with inhibition of IFN signaling. The finding adds to our understanding of the immunopathological mechanisms of severe acute respiratory syndrome coronavirus 2 infection and provides potential therapeutic targets and strategies.


2020 ◽  
Author(s):  
Xueyan Xi ◽  
Yang Guo ◽  
Min Zhu ◽  
Yuhui Wei ◽  
Gang Li ◽  
...  

Abstract Background: Chemokine levels in severe coronavirus disease 2019 (COVID-19) patients have been shown to be markedly elevated. But the role of chemokines in mild COVID-19 has not yet been established. According to the epidemiological statistics, most of the COVID-19 cases in Shiyan City, China, have been mild. The purpose of this study was to evaluate the level of chemokines in mild COVID-19 patients and explore the correlation between chemokines and host immune response.Methods: In this study, we used an enzyme-linked immunosorbent assay (ELISA) to detect serum levels of chemokines in COVID-19 patients in Shiyan City. Expression of chemokine receptors and of other signaling molecules was measured by real-time polymerase chain reaction (PCR).Results: We first demonstrated that COVID-19 patients, both sever and mild cases, are characterized by higher level of chemokines. Specifically, monocyte chemotactic protein 1 (MCP-1) is expressed at higher levels both in severe and mild cases of COVID-19. The receptor of MCP-1, C-C chemokine receptor type 2 (CCR2), was expressed at higher levels in mild COVID-19 patients. Finally, we observed a significant negative correlation between expression levels of interferon (IFN) regulatory factor 3 (IRF3) and serum levels of MCP-1 in mild COVID-19 patients.Conclusion: Higher expression of MCP-1 in mild COVID-19 patients might be correlated with inhibition of IFN signaling. The finding adds to our understanding of the immunopathological mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and provides potential therapeutic targets and strategies.


2020 ◽  
Author(s):  
Xueyan Xi ◽  
Yang Guo ◽  
Min Zhu ◽  
Yuhui Wei ◽  
Gang Li ◽  
...  

Abstract Background: Chemokine levels in severe coronavirus disease 2019 (COVID-19) patients have been shown to be markedly elevated. But the role of chemokines in mild COVID-19 has not yet been established. According to the epidemiological statistics, most of the COVID-19 cases in Shiyan City, China, have been mild. The purpose of this study was to evaluate the level of chemokines in mild COVID-19 patients and explore the correlation between chemokines and host immune response. Methods: In this study, we used an enzyme-linked immunosorbent assay (ELISA) to detect serum levels of chemokines in COVID-19 patients in Shiyan City. Expression of chemokine receptors and of other signaling molecules was measured by real-time polymerase chain reaction (PCR). Results: We first demonstrated that COVID-19 patients, both sever and mild cases, are characterized by higher level of chemokines. Specifically, monocyte chemotactic protein 1 (MCP-1) is expressed at higher levels both in severe and mild cases of COVID-19. The receptor of MCP-1, C-C chemokine receptor type 2 (CCR2), was expressed at higher levels in mild COVID-19 patients. Finally, we observed a significant negative correlation between expression levels of interferon (IFN) regulatory factor 3 (IRF3) and serum levels of MCP-1 in mild COVID-19 patients. Conclusion: Higher expression of MCP-1 in mild COVID-19 patients might be correlated with inhibition of IFN signaling. The finding adds to our understanding of the immunopathological mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and provides potential therapeutic targets and strategies.


Open Medicine ◽  
2007 ◽  
Vol 2 (3) ◽  
pp. 271-279 ◽  
Author(s):  
Koray Ergunay ◽  
Gulcin Altinok ◽  
Bora Gurel ◽  
Ahmet Pinar ◽  
Arzu Sungur ◽  
...  

AbstractIntrauterine Parvovirus B19 infections may cause fetal anemia, non-immune hydrops fetalis or abortion. This study focuses on the pathogenic role of Parvovirus B19 in non-immune hydrops fetalis at Hacettepe University, a major reference hospital in Turkey. Twenty-two cases of non-immune hydrops fetalis were retrospectively selected out of a total of 431 hydrops fetalis specimens from the Department of Pathology archieves. Paraffine embedded tissue sections from placental and liver tissues from each case were evaluated by histopathology, immunohistochemistry, nested PCR and commercial quantitative Real-time PCR. Viral DNA was detected in placental tissues by Real-time PCR in 2 cases (2/22, 9.1%) where histopathology also revealed changes suggestive of Parvovirus B19 infection. No significant histopathologic changes were observed for the remaining sections. Nested PCR that targets the VP1 region of the viral genome and immunohistochemistry for viral capsid antigens were negative for all cases. As a result, Parvovirus B19 is identified as the etiologic agent for the development of non-immune hydrops fetalis for 9.1% of the cases in Hacettepe University, Turkey. Real-time PCR is observed to be an effective diagnostic tool for nucleic acid detection from paraffine embedded tissues. Part of this study was presented as a poster at XIIIth International Congress of Virology, San Francisco, USA (Abstract V-572).


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