Influence of IL-24 on monocyte activity in patients with non-small cell lung cancer / 中华微生物学和免疫学杂志

ABSTRACT

Objective:To investigate the influence of IL-24 on monocyte activity in patients with non-small cell lung cancer (NSCLC) in vitro. Methods:Twenty-five NSCLC patients and 20 healthy controls were enrolled in the current study. Peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) samples were collected to isolate monocytes. Expression of IL-22R1, IL-20R1 and IL-20R2 at mRNA level in monocytes was semi-quantified by real-time RT-PCR. Flow cytometry was used to detect the expression of Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and enzyme linked immunosorbent assay was performed to measure the levels of granzyme A, granzyme B and granzyme H after stimulating monocytes with recombinant human IL-24 (10 ng/ml and 100 ng/ml). The monocytes isolated from peripheral blood of NSCLC patients were co-cultured with A549 cells in vitro. Monocyte-induced target cell death in response to IL-24 stimulation was investigated and changes in the cytotoxicity of monocytes were also assessed after inhibiting granzyme B with Z-AAD-CMK. Student′s t test or LSD- t test was used for comparison. Results:IL-22R1 mRNA was not detected in monocytes. There were no remarkable differences in either IL-20R1 mRNA or IL-20R2 mRNA expression in monocytes between healthy controls and NSCLC patients, or between non-tumor site and tumor site ( P>0.05). FasL and TRAIL expression and granzyme secretion were significantly reduced in monocytes from peripheral blood and tumor sites of NSCLC patients as compared with those from controls ( P<0.05). IL-24 stimulation did not affect the expression of FasL or TRAIL or the secretion of granzyme A or granzyme H ( P>0.05). Low concentration of IL-24 (10 ng/ml) did not affect granzyme B secretion ( P>0.05), while high concentration of IL-24 (100 ng/ml) significantly elevated the secretion of granzyme B by monocytes ( P<0.05). Low concentration of IL-24 (10 ng/ml) did not affect the monocyte-induced target cell death ( P>0.05), while high concentration of IL-24 (100 ng/ml) promoted NSCLC patient-derived monocyte-induced target cell death ( P<0.05). Z-AAD-CMK stimulation suppressed the high concentration of IL-24-mediated elevation of monocyte cytolytic function ( P<0.05). Conclusions:High concentration of IL-24 promoted the cytolytic function of monocytes in NSCLC patients through elevating granzyme B secretion in vitro. However, IL-24 might not influence monocyte function in vivo.