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      Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF‐κB signaling pathway

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          Abstract

          Background

          Influenza A viruses ( IAV) result in severe public health problems with worldwide each year. Overresponse of immune system to IAV infection leads to complications, and ultimately causing morbidity and mortality.

          Objective

          Curcumin has been reported to have anti‐inflammatory ability. However, its molecular mechanism in immune responses remains unclear.

          Methods

          We detected the pro‐inflammatory cytokine secretion and nuclear factor kappa‐light‐chain‐enhancer of activated B cell ( NF‐κB)‐related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment.

          Results

          We found that the IAV infection caused a dramatic enhancement of pro‐inflammatory cytokine productions of human macrophages and mice immune cells. However, curcumin treatment after IAV infection downregulated these cytokines production in a dose‐dependent manner. Moreover, the NF‐κB has been activated in human macrophages after IAV infection, while administration of curcumin inhibited NF‐κB signaling pathway via promoting the expression of nuclear factor of kappa light polypeptide gene enhancer in B‐cells inhibitor, alpha (IκBα), and inhibiting the translocation of p65 from cytoplasm to nucleus.

          Conclusions

          In summary, IAV infection could result in the inflammatory responses of immune cells, especially macrophages. Curcumin has the therapeutic potentials to relieve these inflammatory responses through inhibiting the NF‐κB signaling pathway.

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          Most cited references28

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          Innate immunity to influenza virus infection.

          Influenza viruses are a major pathogen of both humans and animals. Recent studies using gene-knockout mice have led to an in-depth understanding of the innate sensors that detect influenza virus infection in a variety of cell types. Signalling downstream of these sensors induces distinct sets of effector mechanisms that block virus replication and promote viral clearance by inducing innate and adaptive immune responses. In this Review, we discuss the various ways in which the innate immune system uses pattern recognition receptors to detect and respond to influenza virus infection. We consider whether the outcome of innate sensor stimulation promotes antiviral resistance or disease tolerance, and propose rational treatment strategies for the acute respiratory disease that is caused by influenza virus infection.
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            1918 Influenza: the Mother of All Pandemics

            The "Spanish" influenza pandemic of 1918–1919, which caused ≈50 million deaths worldwide, remains an ominous warning to public health. Many questions about its origins, its unusual epidemiologic features, and the basis of its pathogenicity remain unanswered. The public health implications of the pandemic therefore remain in doubt even as we now grapple with the feared emergence of a pandemic caused by H5N1 or other virus. However, new information about the 1918 virus is emerging, for example, sequencing of the entire genome from archival autopsy tissues. But, the viral genome alone is unlikely to provide answers to some critical questions. Understanding the 1918 pandemic and its implications for future pandemics requires careful experimentation and in-depth historical analysis.
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              Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice.

              Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice.
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                Author and article information

                Contributors
                liuling15050673602@126.com
                Journal
                Influenza Other Respir Viruses
                Influenza Other Respir Viruses
                10.1111/(ISSN)1750-2659
                IRV
                Influenza and Other Respiratory Viruses
                John Wiley and Sons Inc. (Hoboken )
                1750-2640
                1750-2659
                11 July 2017
                September 2017
                : 11
                : 5 ( doiID: 10.1111/irv.2017.11.issue-5 )
                : 457-463
                Affiliations
                [ 1 ] Department of Respiration Medicine The Affiliated Wuxi Second People's Hospital of Nanjing Medical University Wuxi China
                Author notes
                [*] [* ] Correspondence

                Ling Liu, Department of Respiration Medicine, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, Wuxi, China.

                Email: liuling15050673602@ 123456126.com

                Author information
                http://orcid.org/0000-0002-4148-4991
                Article
                IRV12459
                10.1111/irv.12459
                5596526
                28646616
                1db20bfd-1e20-4f26-a367-050baefe204b
                © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 June 2017
                Page count
                Figures: 5, Tables: 0, Pages: 7, Words: 4726
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                irv12459
                September 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.9 mode:remove_FC converted:13.09.2017

                Infectious disease & Microbiology
                acute lung injury,curcumin,inflammation,influenza a viruses (iav),nuclear factor kappa‐light‐chain‐enhancer of activated b cells (nf‐κb)

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