Anti-high mobility group box 1 monoclonal antibody suppressed hyper-permeability and cytokine production in human pulmonary endothelial cells infected with influenza A virus

Takahiro Namba, Mitsuru Tsuge, Masato Yashiro, Yukie Saito, Keyue Liu, Masahiro Nishibori, Tsuneo Morishima, Hirokazu Tsukahara

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: High mobility group box-1 (HMGB1) has been reported to be involved in influenza A virus-induced acute respiratory distress syndrome (ARDS). We studied the efficacy of an anti-HMGB1 mAb using an in vitro model of TNF-α stimulation or influenza A virus infection in human pulmonary microvascular endothelial cells (HMVECs). Methods: Vascular permeability of HMVECs was quantified using the Boyden chamber assay under tumor necrosis factor-α (TNF-α) stimulation or influenza A virus infection in the presence of anti-HMGB1 mAb or control mAb. The intracellular localization of HMGB1 was assessed by immunostaining. Extracellular cytokine concentrations and intracellular viral mRNA expression were quantified by the enzyme-linked immunosorbent assay and quantitative reverse transcription PCR, respectively. Results: Vascular permeability was increased by TNF-α stimulation or influenza A infection; HMVECs became elongated and the intercellular gaps were extended. Anti-HMGB1 mAb suppressed both the increase in permeability and the cell morphology changes. Translocation of HMGB1 to the cytoplasm was observed in the non-infected cells. Although anti-HMGB1 mAb did not suppress viral replication, it did suppress cytokine production in HMVECs. Conclusion: Anti-HMGB1 mAb might be an effective therapy for severe influenza ARDS.

Original languageEnglish
Pages (from-to)1101-1111
Number of pages11
JournalInflammation Research
Volume70
Issue number10-12
DOIs
Publication statusAccepted/In press - 2021
Externally publishedYes

Keywords

  • Acute respiratory distress syndrome
  • Cytokine
  • High mobility group box 1
  • Human pulmonary microvascular endothelial cell
  • Influenza
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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