title: Ability of recombinant human catalase to suppress inflammation of the murine lung induced by influenza A.
abstract: Influenza A virus pandemics and emerging antiviral resistance highlight the urgent need for novel generic pharmacological strategies that reduce both viral replication and inflammation of the lung. We have previously investigated the therapeutic efficacy of recombinant human catalase (rhCAT) against viral pneumonia in mice, but the protection mechanisms involved were not explored. In the present study, we have performed a more in-depth analysis covering survival, lung inflammation, immune cell responses, production of cytokines, and inflammation signaling pathways in mice. Male imprinting control region mice were infected intranasally with high pathogenicity (H1N1) influenza A virus followed by treatment with recombinant human catalase. The administration of rhCAT resulted in a significant reduction in inflammatory cell infiltration (e.g., macrophages and neutrophils), inflammatory cytokine levels (e.g., IL-2, IL-6, TNF-α, IFN-γ), the level of the intercellular adhesion molecule 1 chemokine and the mRNA levels of toll-like receptors TLR-4, TLR-7, and NF-κB, as well as partially maintaining the activity of the antioxidant enzymes system. These findings indicated that rhCAT might play a key protective role in viral pneumonia of mice via suppression of inflammatory immune responses.
authors.affiliation: Department of Drug Biosynthesis, School of Pharmacy, Fudan University, 826 Zhang Heng Road, Shanghai, 201203, China, xunlongshi@fudan.edu.cn.
authors.forename: Xunlong
authors.initials: X
authors.lastname: Shi
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Shi
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Hongguang
authors.initials: H
authors.lastname: Zhu
authors.forename: Pei
authors.initials: P
authors.lastname: Zhou
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Dianwen
authors.initials: D
authors.lastname: Ju
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D008168:Lung / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D018384:Oxidative Stress / Q000276:immunology; D011024:Pneumonia, Viral / Q000188:drug therapy*; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D008315:Malondialdehyde; D002374:Catalase