High mobility group box-1 (HMGB-1) and its receptors in the pathogenesis of malaria-associated acute lung injury/acute respiratory distress syndrome in a mouse model

Tachpon Techarang; Pitchanee Jariyapong; Parnpen Viriyavejakul; Chuchard Punsawad

doi:10.1016/j.heliyon.2021.e08589

High mobility group box-1 (HMGB-1) and its receptors in the pathogenesis of malaria-associated acute lung injury/acute respiratory distress syndrome in a mouse model

Heliyon. 2021 Dec 11;7(12):e08589. doi: 10.1016/j.heliyon.2021.e08589. eCollection 2021 Dec.

Authors

Tachpon Techarang^{1

2}, Pitchanee Jariyapong¹, Parnpen Viriyavejakul³, Chuchard Punsawad^{1

2}

Affiliations

¹ Department of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat 80160, Thailand.
² Research Center in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, Thailand.
³ Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

Abstract

The DNA-binding protein high mobility group box-1 (HMGB-1) mediates proinflammatory cytokines that contribute to acute lung injury (ALI). Although ALI is a frequent complication of malaria infection, the contribution of HMGB-1 and its receptors to the pathogenesis of malaria-associated ALI/acute respiratory distress syndrome (MA-ALI/ARDS) has not been investigated in a mouse model. Here, the malaria-infected mice were divided into two groups according to lung injury score: the ALI/ARDS and non-ALI/ARDS groups. The expression of HMGB-1 and its receptors (RAGE, TLR-2 and TLR-4) in lung tissues was investigated by using immunohistochemical staining and real-time polymerase chain reaction (PCR). Additionally, HMGB-1 and proinflammatory cytokine (TNF-α, IFN-γ, IL-1 and IL-6) levels in plasma and lung tissues were quantified by using enzyme-linked immunosorbent assays. Cellular expression of both HMGB-1 and its receptors (RAGE, TLR-2 and TLR-4) was significantly increased in the lung tissues of the ALI/ARDS group compared with those in the non-ALI/ARDS and control groups. The levels of HMGB-1, TNF-α, IFN-γ, IL-1 and IL-6 were significantly increased in both plasma and lung tissues of the ALI/ARDS group compared with those in the non-ALI/ARDS and control groups, which were similar to the results obtained by real-time PCR. Increased mRNA expression of RAGE, TLR-2 and TLR-4 was found in the lung tissues of the ALI/ARDS group. Furthermore, the plasma HMGB-1 level was positively correlated with TLR-4 mRNA expression in the ALI/ARDS group. HMGB-1 levels were significantly increased in plasma and lung tissues of MA-ALI/ARDS mice and were related to the upregulated expression of HMGB-1 and proinflammatory cytokines. In conclusion, this study demonstrates that HMGB-1 is an important mediator of MA-ALI/ARDS pathogenesis and may represent a target for therapeutic malaria interventions with ALI/ARDS.

Keywords: Acute lung injury; Acute respiratory distress syndrome; HMGB-1; Malaria.