Summary Growing evidence shows that a homozygous 6·7-kb deletion of the novel anti-inflammatory molecule leukocyte immunoglobulin-like receptor A3 (LILRA3) is associated with many autoimmune disorders. However, its effects on pathogenesis of inflammatory bowel disease (IBD) have yet not been clarified. LILRA3 is mainly expressed in monocytes, whereas its effects on biological behaviors of monocytes have not been systematically reported. In our study, to investigate the association between LILRA3 polymorphism and IBD susceptibility, LILRA3 polymorphism was assessed in 378 IBD patients and 509 healthy controls. Quantitative real time PCR (qRT–PCR), Western blot and immunohistochemistry (IHC) were employed to detect the LILRA3 expression in IBD patient blood and intestinal samples. The human U937 monocyte cell line was employed to establish LILRA3 over-expressing cells and the effects of LILRA3 on the biological behaviors of U937 cells were systematically explored. Although no association of the polymorphism with IBD development was found, LILRA3 expression was markedly increased in IBD patients compared with healthy controls. Over-expression of LILRA3 in monocytes led to significant decreases in secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-6. Additionally, LILRA3 abated monocyte migration by reducing the expression of several chemokines and enhanced monocyte phagocytosis by increasing CD36 expression. Furthermore, LILRA3 promoted monocyte proliferation through a combination of Akt and extracellular receptor kinase/mitogen-activated protein kinase (Erk/MEK) signaling pathways. We report for the first time, to our knowledge, that LILRA3 is related to IBD and functions as an anti-inflammatory modulator in U937 cells.

We investigated the significance of cytokines (soluble interleukin‐2 receptor, granulocyte‐macrophage colony‐stimulating factor, interleukin‐6, and interferon‐gamma) and CD68‐positive microparticles in immune thrombocytopenic purpura. Cytokines were measured by enzyme‐linked immunosorbent assay and microparticles were detected by flow cytometry. CD68 expression by histiocytic U937 cells incubated with lipopolysaccharide or cytokines was also assessed in a control study. The level of CD68‐positive microparticles was significantly higher in the patients with thrombocytopenia than in normal controls (p<0.01). The soluble interleukin‐2 receptor level was also significantly higher in patients than in controls (p<0.01), but the other cytokines did not show a significant difference. However, patients with severe thrombocytopenia (platelet count >20000/μl) had significantly higher levels of granulocyte‐macrophage colony‐stimulating factor and interleukin‐6 than the controls (p<0.05). When opsonized platelets were incubated with activated U937 cells, lipopolysaccharide and granulocyte‐macrophage colony‐stimulating factor caused an increase of CD68‐positive microparticles in the supernatant. These results suggest that granulocyte‐macrophage colony‐stimulating factor is released by activated T cells in immune thrombocytopenic purpura and activates monocyte/macrophage phagocytosis, resulting in an increase of circulating CD68‐positive microparticles and enhanced platelet destruction.