Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

Chan, Michael Chi Wai; Cheung, Chung Yan; Chui, Wing Hung; Tsao, Sai Wah; Nicholls, John M.; Chan, Yuen-Yan; Chan, Renee W. Y.; Long, Hoang Thuy; Poon, Leo L. M.; Guan, Yi; Peiris, J S Malik

doi:10.1186/1465-9921-6-135

Cited by 456 publications

(416 citation statements)

References 38 publications

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“…Increased viral replication competence, capacity for dissemination beyond the respiratory tract, and unusual tissue tropism have all been proposed to be relevant to pathogenesis (1). In addition to these mechanisms, there is in vitro and in vivo evidence that cytokine dysregulation contributes to the pathogenesis of human H5N1 disease (2)(3)(4)(5).…”

Section: Induction Of Proinflammatory Cytokines In Primary Humanmentioning

confidence: 99%

“…Humans and mice infected with H5N1 viruses have markedly elevated numbers of macrophages in the lung (4,8). When compared with human influenza virus (e.g., H1N1)-infected macrophages in vitro, H5N1 virus-infected human primary macrophages produce higher levels of cytokines and chemokines such as TNF-␣, IFN-␤, IL-6, IL-1␤, CXCL10/IFN-␥-inducible protein 10 (IP-10), 3 CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1␣, and CCL4/MIP-1␤ (2,8,9). Similarly, H5N1 viruses hyperinduce chemokines such as IP-10 and MCP-1 from primary respiratory epithelial cells in vitro (3).…”

Section: Induction Of Proinflammatory Cytokines In Primary Humanmentioning

confidence: 99%

“…When compared with human influenza virus (e.g., H1N1)-infected macrophages in vitro, H5N1 virus-infected human primary macrophages produce higher levels of cytokines and chemokines such as TNF-␣, IFN-␤, IL-6, IL-1␤, CXCL10/IFN-␥-inducible protein 10 (IP-10), 3 CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1␣, and CCL4/MIP-1␤ (2,8,9). Similarly, H5N1 viruses hyperinduce chemokines such as IP-10 and MCP-1 from primary respiratory epithelial cells in vitro (3). H5N1 virus genotypes differ in their capacity to induce cytokines in vitro (9), but the precise viral and genetic determinants underlying this high cytokine inducing phenotype are not well understood.…”

Section: Induction Of Proinflammatory Cytokines In Primary Humanmentioning

confidence: 99%

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Induction of Proinflammatory Cytokines in Primary Human Macrophages by Influenza A Virus (H5N1) Is Selectively Regulated by IFN Regulatory Factor 3 and p38 MAPK

Hui

Lee

Cheung

et al. 2009

The Journal of Immunology

134

116

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The hyperinduction of proinflammatory cytokines and chemokines such as TNF-α, IFN-β, and CCL2/MCP-1 in primary human macrophages and respiratory epithelial cells by the highly pathogenic avian influenza H5N1 is believed to contribute to the unusual severity of human H5N1 disease. Here we show that TNF-α, IFN-β, and IFN-λ1 are the key mediators directly induced by the H5N1 virus in primary human macrophages. In comparison with human influenza (H1N1), the H5N1 virus more strongly activated IFN regulatory factor 3 (IRF3). IRF3 knockdown and p38 kinase inhibition separately and in combination led to a substantial reduction of IFN-β, IFN-λ1, and MCP-1 but only to a partial reduction of TNF-α. IRF3 translocation was independent of p38 kinase activity, indicating that IRF3 and p38 kinase are distinct pathways leading to cytokine production by H5N1 virus. We conclude that IRF3 and p38 kinase separately and predominantly contribute to H5N1-mediated induction of IFN-β, IFN-λ1, and MCP-1 but only partly control TNF-α induction. A more precise identification of the differences in the regulation of TNF-α and IFN-β could provide novel targets for the design of therapeutic strategies for severe human H5N1 influenza and also for treating other causes of acute respiratory distress syndrome.

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Section: Induction Of Proinflammatory Cytokines In Primary Humanmentioning

confidence: 99%

Section: Induction Of Proinflammatory Cytokines In Primary Humanmentioning

confidence: 99%

Section: Induction Of Proinflammatory Cytokines In Primary Humanmentioning

confidence: 99%

See 1 more Smart Citation

Induction of Proinflammatory Cytokines in Primary Human Macrophages by Influenza A Virus (H5N1) Is Selectively Regulated by IFN Regulatory Factor 3 and p38 MAPK

Hui

Lee

Cheung

et al. 2009

The Journal of Immunology

134

116

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“…The underlying mechanisms of influenzarelated acute lung injury remain unclear, and effective therapies are lacking. Viruses that are highly pathogenic to humans (e.g., H5N1 viruses) may differ intrinsically from the less pathogenic (LP) (e.g., seasonal H1N1) viruses in their replication competence, cell tropism, and/or cytokine dysregulation (1,2). Early treatment of H5N1 disease with the antiinfluenza drug oseltamivir is helpful but does not ensure a favorable outcome (3).…”

mentioning

confidence: 99%

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Chan

Kuok

Leung

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

181

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Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

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“…Direct contact with pathogenic materials such as excreta or secretion of poultry seems to cause infection of H5N1 to human. H5N1 has been reported to cause human respiratory problems, fever, pneumonia, and relatively severe cytokine releases [9].…”

Section: H5n1mentioning

confidence: 99%

Treatment of various avian influenza virus based on comparison using decision tree algorithm

2016

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Abstract.Recently, the world is full of anxiety about AI(Avian Influenza). Among Avian Influenza virus subtypes, H5N1 is considered the most threatening to not only birds, but also humans as numerous human cases with high mortality have been reported. Unlike H7N9, which has not been reported infect humans, H5N8 also became infectious to humans due to dramatic mutation. As human infection cases of AI have increased, numerous researchers have been trying to develop an effective treatment against them. Thus, our project group decided to analyze the similarity and difference of H5N1, H5N8, and H7N9, since it would be useful for finding effective treatment of AI, using Decision Tree Algorithm which figures out distinctive factors of given dataset for comparing protein sequences of each viruses. The comparison using Decision Tree Algorithm, which indicates correlation among H5N1, H5N8, and H7N9, will be effective on narrowing the range of attempts on developing treatment for Avian Influenza virus.

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Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

Cited by 456 publications

References 38 publications

Induction of Proinflammatory Cytokines in Primary Human Macrophages by Influenza A Virus (H5N1) Is Selectively Regulated by IFN Regulatory Factor 3 and p38 MAPK

Induction of Proinflammatory Cytokines in Primary Human Macrophages by Influenza A Virus (H5N1) Is Selectively Regulated by IFN Regulatory Factor 3 and p38 MAPK

Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

Treatment of various avian influenza virus based on comparison using decision tree algorithm

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