Annexin A1‑mediated inhibition of inflammatory cytokines may facilitate the resolution of inflammation in acute radiation‑induced lung injury

Abstract

The present study evaluated the role of annexin A1 (ANXA1) in the treatment of acute radiation-induced lung injury (RILI) and investigated the mechanism of its action. The expression of ANXA1, interleukin-6 (IL-6) and myeloperoxidase (MPO) in the plasma of patients with RILI prior to and following hormonotherapy was assessed by enzyme-linked immunosorbent assay. The association of plasma ANXA1 concentration with clinical effect, and the correlation between the expression of ANXA1 and that of IL-6 and MPO were evaluated. ANXA1 was overexpressed or knocked down in a macrophage cell line, and its impact on IL-6 and MPO expression was measured. Following glucocorticoid hormonotherapy, patients with RILI exhibited a higher plasma concentration of ANXA1 compared with that prior to treatment, while IL-6 and MPO levels were lower. The concentration of ANXA1 in plasma was negatively correlated with IL-6 and MPO levels, with a correlation coefficient of-0.492 and-0.437, respectively (P<0.001). The increasing concentration of ANXA1 in plasma following treatment was associated with the clinical effect in patients with RILI (P= 0.007). The expression levels of of IL-6 and MPO were inhibited both in the cytoplasm and in the culture solution, when ANXA1 expression was upregulated in a macrophage cell line. In conclusion, ANXA1 inhibited the synthesis and secretion of IL-6 and MPO inflammatory cytokines, indicating that ANXA1 may have therapeutic potential as a treatment target for RILI.

Role of DAMPs in respiratory virus-induced acute respiratory distress syndrome—with a preliminary reference to SARS-CoV-2 pneumonia

“…In those patients with mild or moderate ARDS who do not proceed to or survive the severe course of ARDS, a resolution of inflammation can be observed, characterized by fluid clearance and solute reabsorption from the alveolus [ 133 , 134 ]. SAMPs such as AnxA1 [ 135 ] and SPMs [ 136 ] have already been reported to be involved in these processes. Several mechanisms central to controlling the resolution of lung inflammation have been discussed, including enhanced efferocytosis of apoptotic neutrophils/eosinophils performed by antiinflammatory and/or proresolving macrophages.…”

Mechanisms and Clinical Applications of Glucocorticoid Steroids in Muscular Dystrophy

“…Lipocortin 1 (also known as Annexin A1) is a strong anti-inflammatory effector whose expression is driven by glucocorticoids [45]. High levels of annexin A1 suppress proinflammatory genes including IL-6, COX-2, and iNOS [46][47][48][49]. In the presence of glucocorticoids, annexin A1 is upregulated in myeloid cells where it dynamically hinders inflammatory responses.…”

Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes

“…Recently, the function of ANXA1 in the therapy of acute radiation-induced lung injury has been analyzed and the mechanism of its action is investigated (149). The role of damage-associated molecular patterns in neuro-inflammation has been implicated in adverse neurological outcomes following lethal hemorrhagic shock and polytrauma.…”