tetano
Editor, Senior Moderator
Inflamm Res
. 2021 Aug 29.
doi: 10.1007/s00011-021-01496-5. Online ahead of print.
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[SUP] 1 [/SUP], Mitsuru Tsuge[SUP] 2 [/SUP], Masato Yashiro[SUP] 1 [/SUP], Yukie Saito[SUP] 1 [/SUP], Keyue Liu[SUP] 3 [/SUP], Masahiro Nishibori[SUP] 3 [/SUP], Tsuneo Morishima[SUP] 4 [/SUP], Hirokazu Tsukahara[SUP] 1 [/SUP]
Affiliations
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.
Keywords: Acute respiratory distress syndrome; Cytokine; High mobility group box 1; Human pulmonary microvascular endothelial cell; Influenza; Tumor necrosis factor-α.
. 2021 Aug 29.
doi: 10.1007/s00011-021-01496-5. Online ahead of print.
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[SUP] 1 [/SUP], Mitsuru Tsuge[SUP] 2 [/SUP], Masato Yashiro[SUP] 1 [/SUP], Yukie Saito[SUP] 1 [/SUP], Keyue Liu[SUP] 3 [/SUP], Masahiro Nishibori[SUP] 3 [/SUP], Tsuneo Morishima[SUP] 4 [/SUP], Hirokazu Tsukahara[SUP] 1 [/SUP]
Affiliations
- PMID: 34455489
- DOI: 10.1007/s00011-021-01496-5
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.
Keywords: Acute respiratory distress syndrome; Cytokine; High mobility group box 1; Human pulmonary microvascular endothelial cell; Influenza; Tumor necrosis factor-α.