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. 2021 Jul-Sep;16(3):366-376.
doi: 10.18502/ijpa.v16i3.7089.

Protective Effect of an Anti-HMGB-1 Neutralizing Antibody on Hemozoin-Induced Alveolar Epithelial Cell in a Model of Malaria Associated ALI/ARDS

Tachpon Techarang  1   2 , Pitchanee Jariyapong  1 , Parnpen Viriyavejakul  3 , Supattra Glaharn  3 , Charit Srisook  3 , Chuchard Punsawad  1   2
Affiliations

Protective Effect of an Anti-HMGB-1 Neutralizing Antibody on Hemozoin-Induced Alveolar Epithelial Cell in a Model of Malaria Associated ALI/ARDS

Tachpon Techarang et al. Iran J Parasitol. 2021 Jul-Sep.

Abstract

Background: We aimed to determine whether neutralizing high mobility group box-1 (HMGB-1) prevents the release of HMGB-1 and proinflammatory cytokines on hemozoin (Hz)-induced alveolar epithelial cell in a model of malaria associated ALI/ARDS.

Methods: This study was conducted in the Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand in 2020. Human pulmonary alveolar epithelial cells (HPAEpiCs) were exposed to medium alone or 20 μM Hz for 24 h and incubated with different concentrations (1, 5, and 10 μg/ml) of anti-HMGB-1 monoclonal antibody (mAb) for various times (0, 4, 12, 24, and 48 h). The levels of HMGB-1, TNF-α and IFN-γ in the supernatants were measured by ELISA. The mRNA expression of RAGE, TLR-2 and TLR-4 were analyzed by real-time PCR.

Results: The HPAEpiCs treated with 10 μg/ml anti-HMGB-1 mAb showed a significant reduction in HMGB-1 release into the supernatant compared with those treated with 1 and 5 μg/ml anti-HMGB-1 mAb. The levels of TNF-α and IFN-γ were significantly decreased in the supernatant of HPAEpiCs treated with 1, 5, and 10 μg/ml anti-HMGB-1 mAb for 4, 12, 24, and 48 h compared with those stimulated with Hz alone. The mRNA expression levels of RAGE, TLR-2, and TLR-4 were significantly decreased after 24 h of anti-HMGB-1 antibody treatment at all concentrations.

Conclusion: An anti-HMGB-1 antibody could be an effective agent for inhibiting the release of HMGB-1, TNF-α and IFN-γ. Furthermore, a neutralizing anti-HMGB-1 antibody could be applicable for the treatment of malaria-associated ALI/ARDS.

Keywords: Acute lung injury; HMGB1 protein; Malaria.

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Conflict of interest statement

Conflict of interest The authors declared that there is no conflict of interest.

Figures

Fig. 1:
Fig. 1:
Levels of HMGB-1 in the culture supernatant of human pulmonary alveolar epithelial cells (HPAEpiCs) after stimulation with 20 μM synthetic Hz and treatment with different concentrations (1, 5, and 10 μg/ml) of anti-HMGB-1 monoclonal antibody for different times (0, 4, 12, 24, and 48 h). The levels of HMGB-1 were measured by ELISA. The data are expressed as the mean ± SEM of 3 independent experiments
Fig. 2:
Fig. 2:
The levels of TNF-α and IFN-γ in the culture supernatant of human pulmonary alveolar epithelial cells (HPAEpiCs) after stimulation with 20 μM synthetic Hz and treatment with different concentrations (1, 5, and 10 μg/ml) of anti-HMGB-1 monoclonal antibody for different times (0, 4, 12, 24, and 48 h). (a) The level of TNF-α in the culture supernatant. (b) The level of IFN-γ in the culture supernatant. The data are expressed as the mean ± SEM of 3 independent experiments
Fig. 3:
Fig. 3:
The mRNA expression of RAGE, TLR-2 and TLR-4 in human pulmonary alveolar epithelial cells (HPAEpiCs) after stimulation with 20 μM synthetic Hz and treatment with different concentrations (1, 5, and 10 μg/ml) of anti-HMGB-1 monoclonal antibody for different times (0, 4, 12, 24, and 48 h). (a) The mRNA expression of RAGE. (b) The mRNA expression of TLR-2. (c) The mRNA expression of TLR-4. The data are expressed as the mean ± SEM of 3 independent experiments. *P<0.05
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