JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infection

Since the twentieth century, four influenza pandemics caused by IAV have killed millions of people worldwide. IAV infection could induce acute lung injury mediated by cytokine storms, which is an essential cause of death in critically ill patients. Consequently, it is crucial to explore the regulato...

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Main Authors: Na Chen, Jiayu Jin, Bingchen Qiao, Zihe Gao, Yusen Tian, Jihui Ping
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Virus Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0168170225000541
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author Na Chen
Jiayu Jin
Bingchen Qiao
Zihe Gao
Yusen Tian
Jihui Ping
author_facet Na Chen
Jiayu Jin
Bingchen Qiao
Zihe Gao
Yusen Tian
Jihui Ping
author_sort Na Chen
collection DOAJ
description Since the twentieth century, four influenza pandemics caused by IAV have killed millions of people worldwide. IAV infection could induce acute lung injury mediated by cytokine storms, which is an essential cause of death in critically ill patients. Consequently, it is crucial to explore the regulators and regulatory mechanisms of cytokine storms, which may provide potential drug targets and expand our understanding of acute lung injury. Previous studies have shown that JNK kinase is essential in promoting inflammatory responses during viral infections. In this study, we demonstrated that JNK kinase could regulate the IAV-induced cytokine storms by affecting the expression of pro-inflammatory and anti-inflammatory factors. Further studies revealed that inhibition of JNK kinase activity significantly downregulated the expression of the inflammatory amplifier TREM1. Besides, TREM1 knockdown could significantly inhibit the expression of pro-inflammatory factors. Furthermore, SP600125 is a specific inhibitor of JNK kinase. The results show that TREM1 overexpression reversed the effect of SP600125 treatment on the expression of pro-inflammatory factors. Together, we found that JNK kinase could activate the inflammatory amplifier TREM1 to promote inflammatory responses during influenza A virus infection. These findings may provide some inspiration for subsequent researchers to explore the regulatory mechanisms of cytokine storms induced by emerging viral infections.
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spelling doaj-art-bebb5a1fa3a943cb9fc6d2e8ae40b21c2025-08-20T03:13:39ZengElsevierVirus Research1872-74922025-06-0135619957710.1016/j.virusres.2025.199577JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infectionNa Chen0Jiayu Jin1Bingchen Qiao2Zihe Gao3Yusen Tian4Jihui Ping5MOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaMOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaCorresponding author.; MOE Joint International Research Laboratory of Animal Health and Food Safety, Engineering Laboratory of Animal Immunity of Jiangsu Province, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaSince the twentieth century, four influenza pandemics caused by IAV have killed millions of people worldwide. IAV infection could induce acute lung injury mediated by cytokine storms, which is an essential cause of death in critically ill patients. Consequently, it is crucial to explore the regulators and regulatory mechanisms of cytokine storms, which may provide potential drug targets and expand our understanding of acute lung injury. Previous studies have shown that JNK kinase is essential in promoting inflammatory responses during viral infections. In this study, we demonstrated that JNK kinase could regulate the IAV-induced cytokine storms by affecting the expression of pro-inflammatory and anti-inflammatory factors. Further studies revealed that inhibition of JNK kinase activity significantly downregulated the expression of the inflammatory amplifier TREM1. Besides, TREM1 knockdown could significantly inhibit the expression of pro-inflammatory factors. Furthermore, SP600125 is a specific inhibitor of JNK kinase. The results show that TREM1 overexpression reversed the effect of SP600125 treatment on the expression of pro-inflammatory factors. Together, we found that JNK kinase could activate the inflammatory amplifier TREM1 to promote inflammatory responses during influenza A virus infection. These findings may provide some inspiration for subsequent researchers to explore the regulatory mechanisms of cytokine storms induced by emerging viral infections.http://www.sciencedirect.com/science/article/pii/S0168170225000541Influenza A virusJNK kinaseTREM1Inflammatory amplifierInflammatory responses
spellingShingle Na Chen
Jiayu Jin
Bingchen Qiao
Zihe Gao
Yusen Tian
Jihui Ping
JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infection
Virus Research
Influenza A virus
JNK kinase
TREM1
Inflammatory amplifier
Inflammatory responses
title JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infection
title_full JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infection
title_fullStr JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infection
title_full_unstemmed JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infection
title_short JNK kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier TREM1 during influenza a virus infection
title_sort jnk kinase promotes inflammatory responses by inducing the expression of the inflammatory amplifier trem1 during influenza a virus infection
topic Influenza A virus
JNK kinase
TREM1
Inflammatory amplifier
Inflammatory responses
url http://www.sciencedirect.com/science/article/pii/S0168170225000541
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