HA of H1N1 enhanced the expression of ICAM-1 and IL-6 in HUVECs and pathological injury in the lungs in mice

Gene. 2021 Oct 30:801:145854. doi: 10.1016/j.gene.2021.145854. Epub 2021 Jul 16.

Abstract

Objective: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated.

Methods: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively.

Results: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 μg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 μl of HA (50 μg/ml and 100 μg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion.

Conclusions: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.

Keywords: Hemagglutinin; ICAM-1; IL-6; Influenza virus H1N1; Lung injury; Vascular endothelium.

MeSH terms

  • Cells, Cultured
  • Hemagglutinin Glycoproteins, Influenza Virus / physiology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Interleukin-6 / metabolism*
  • Lung / metabolism
  • Lung / pathology*
  • Real-Time Polymerase Chain Reaction

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • ICAM1 protein, human
  • Interleukin-6
  • Intercellular Adhesion Molecule-1