TRIM59 alleviates acute respiratory distress syndrome by regulating inflammatory cytokines through RING domain

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by significant morbidity and mortality. Particularly since the outbreak of COVID-19, the incidence and complexity of ARDS have been further highlighted. The etiology and pathogenesis of ARDS are multifactorial, involving complex interactions among genetic, environmental, and host factors. Further exploration of these factors is essential to enhance our understanding of ARDS and to develop more effective therapeutic strategies. Alveolar macrophages (AMs) are the first line of defense of innate immunity and are key to regulate the immune system, and are closely related to cytokine storm in ARDS. Therefore, macrophages are an important part to alleviate ARDS. TRIM59 is a molecule expressed on macrophages. Our previous studies have shown that TRIM59 was capable of modulating macrophage function. However, the role of TRIM59 in the pathogenesis and progression of ARDS remains to be elucidated. In this study, we established an animal model of ARDS using mice in which TRIM59 was specifically knocked out in bone marrow-derived macrophages (BMDMs). Our results confirmed that TRIM59 exerted a protective effect against ARDS in vivo via its regulation on macrophages. Mechanistic investigations revealed that TRIM59 inhibited the activation of the nuclear factor-κB (NF-κB) signaling pathway through its RING domain. In summary, the present findings indicate that TRIM59 may serve as a crucial regulatory molecule in the ARDS, potentially offering a novel therapeutic target for its alleviation.