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

摘要

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.