Targeting the pro‐inflammatory factor CCL2 (MCP‐1) with Bindarit for influenza A (H7N9) treatment

Wolf, Stefan; Johnson, Scott K.; Perwitasari, Olivia; Mahalingam, Suresh; Tripp, Ralph A.

doi:10.1038/cti.2017.8

Cited by 12 publications

(8 citation statements)

References 50 publications

(92 reference statements)

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“…Higher levels of chemokines, including IP-10, IL-8 and MCP-1, were believed to be associated with the acute respiratory distress syndrome (ARDS) progression and even fatal outcome in patients with H5N1 or H7N9 virus infection [14,50]. Blockade of IP-10 and MCP-1 was proved to significantly lessen the disease severity of influenza virus infection [51,52]. Expression of COX-2 and PGE 2 has been suggested to play a role in enhancing virus-induced inflammation and impairment of host antiviral immunity [39,53].…”

Section: Discussionmentioning

confidence: 99%

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Xiang

Liang

et al. 2020

BMC Complement Med Ther

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Background: Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the antiinflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations.Methods: The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virustriggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. Results: Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E 2 (PGE 2 ) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings.Conclusion: Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.

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Section: Discussionmentioning

confidence: 99%

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Xiang

Liang

et al. 2020

BMC Complement Med Ther

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“…Monocyte chemoattractant protein-1 (MCP-1; also referred to as chemokine [C-C motif] ligand 2 [CCL2]) plays an important role in inflammation [ 13 ]. CCL2 is a small cytokine associated with proinflammation or inflammation and mainly induces acute inflammatory damage in humans under pathological conditions [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

Human CD36 overexpression in renal tubules accelerates the progression of renal diseases in a mouse model of folic acid-induced acute kidney injury

Jung

Choi

Song

et al. 2018

Kidney Res Clin Pract.

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BackgroundAcute kidney injury (AKI) is a risk factor for progression to chronic kidney disease, with even subclinical AKI episodes progressing to chronic kidney disease. Several risk factors such as preexisting kidney disease, hyperglycemia, and hypertension may aggravate renal disease after AKI. However, mechanisms underlying the progression of AKI are still unclear. This study identified the effect of human cluster of differentiation 36 (CD36) overexpression on the progression of folic acid-induced AKI.MethodsPax8–rtTA/tetracycline response element–human CD36 transgenic mice were used to elucidate the effect of human CD36 overexpression in the proximal tubules on folic acid-induced AKI.ResultsResults of histological analysis showed severely dilated tubules with casts and albuminuria in folic acid-treated transgenic mice overexpressing human CD36 compared with folic acid-treated wild-type mice. In addition, analysis of mRNA expression showed a significant increase in the collagen 3a1 gene in folic acid-treated transgenic mice overexpressing human CD 36 compared with folic acid-treated wild type mice.ConclusionHuman CD36-overexpressing transgenic mice showed severe pathological changes and albuminuria compared with wild-type mice. Moreover, mRNA expression of the collagen 3a1 gene increased in folic acid-treated transgenic mice. These results suggest that human CD36 overexpression is a risk factor of AKI and its progression to chronic kidney disease.

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“…The problem of bacterial complications post respiratory viral infections signaling can become an important therapeutic approach to preventing both cytokine storm effects and the development of secondary bacterial complications in the areas adjacent to the respiratory tract [79,82,[103][104][105].…”

Section: Resultsmentioning

confidence: 99%

The problem of bacterial complications post respiratory viral infections

Egorov

2018

Microbiology Independent Research Journal (MIR Journal)

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Every person over the course of their lifetime is repeatedly infected by a variety of respiratory viruses that represent risk factors for the development of bacterial complications. The most dangerous among the etiological factors of acute respiratory viral diseases is the influenza A virus. This virus is capable of causing catastrophic pandemics with high mortality mainly due to secondary bacterial pneumonia. As has been shown in numerous recent studies, the main mechanism of provoking bacterial infections irrespective of the type of respiratory virus is the imbalanced response of the antiviral innate immunity -excessive interferon response and uncontrolled inflammation. The probability of severe bacterial complications in the course of acute respiratory viral infections is determined by both the virulence of the virus itself and by the composition of the respiratory microbiota at the time of the viral infection as well as by the genetic characteristics of the organism. The occurrence of severe bacterial complications is also affected by the chronic diseases that have an impact on the regulation of the innate immune response. This review summarizes the current concept of the mechanisms of the development of post viral bacterial complications as well as the potential prevention strategies for these complications.

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Targeting the pro‐inflammatory factor CCL2 (MCP‐1) with Bindarit for influenza A (H7N9) treatment

Cited by 12 publications

References 50 publications

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings

Human CD36 overexpression in renal tubules accelerates the progression of renal diseases in a mouse model of folic acid-induced acute kidney injury

The problem of bacterial complications post respiratory viral infections

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