title: Proinflammatory effects of the hemagglutinin protein of the avian influenza A (H7N9) virus and microRNA‑mediated homeostasis response in THP‑1 cells.
abstract: The pathology and immunological responses to hemagglutinin (HA) from H7N9 avian influenza viruses in humans remain unclear. The present study aimed to investigate the proinflammatory activity of the HA protein obtained from H7N9 viruses and the mechanisms underlying the homeostasis of microRNAs (miRNAs) in response to inflammatory stimuli. The expression of proinflammatory factors and miRNAs was assayed in the THP‑1 cells using reverse transcription‑quantitative polymerase chain reaction. Results showed that HA significantly increased the expression of interleukin (IL)‑1α, IL‑1β and IL‑6 in the THP‑1 cells. Furthermore, HA and lipopolysaccharide exhibited synergic effects on the expression of IL‑1α, IL‑1β and IL‑6 in the THP‑1 cells. Let‑7e can target IL‑6 and inhibit its expression. Notably, HA significantly increased let‑7e expression in THP‑1 cells and decreased the let‑7e levels in the medium. However, the knockdown of toll‑like receptor 4 (TLR4) significantly attenuated the effects of HA. These results indicate that the HA can induce inflammatory stress and may trigger an miRNA‑mediated homeostasis response to this stress. The effects of HA appeared to be mediated by the TLR4 pathway.
authors.affiliation: Shenzhen Key Lab of Health Science and Technology, Division of Life Science & Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, P.R. China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Central Laboratory of Health Quarantine, International Travel Health Care Center, Shenzhen Entry-exit Inspection and Quarantine Bureau, Shenzhen, Guangdong 518033, P.R. China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Health Inspection and Quarantine, School of Public Health, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Ouyang
authors.affiliation: Shenzhen Key Lab of Health Science and Technology, Division of Life Science & Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Xie
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype; D053582:Interleukin-1alpha / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C508584:IL1A protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D035683:MicroRNAs; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014764:Viral Proteins; C109963:hemagglutinin, avian influenza A virus; C487931:mirnlet7 microRNA, human