509 CCL3L1 Protein Did Not Affect IL-6 Expression, but Significantly Up-regulated IL-10 Expression in the Allergic Response

BACKGROUND: Previously, we found that the mean copy number of CCL3L1 in patients with asthma was significantly lower than that of control subjects (3.13 vs 3.75, P = 0.001). We investigated its possible molecular mechanism using a human monocytic cell line stimulated with house dust mite extract. METHOD: The THP-1 human monocytic cells were stimulated with various concentrations of HDM extract. After stimulation, assay-on-demand gene expression products (Applied Biosystems) were used to evaluate mRNA expression of CCL3L1 (Hs 00609691_ml), IlL-6 (Hs00174131_ml), and IL-10 (Hs00961622_ml) levels as measurement of mRNA levels by real time PCR. RESULTS: Treatment of THP-1 cells with various concentration of HDM extract induced marked up- regulation of the expression of cytokines IL-10 and IL-6, which indicated that allergic responses were efficiently induced. Recombinant CCL3L1 protein had no effect on cytokine expression of THP-1 Cells in absence of HDM extract stimulation. In the presence of HDM extract (10 ug/mL) stimulation, CCL3L1 protein significantly up-regulated IL-10 expression (Ratio to ng/mL CCL3L1) dose-dependantly (0 ug/mL CCL3L1 + 0.3;12.4, 10 ug/mL CCL3L1; 15.8+ 1.1, 50 ug/mL CCL3L1; 16.8+ 0.3, 100 ug/mL CCL3L1; 18.0+ 0.8, (P > 0.05), but did not affect IL-6 expression (P > 0.05). CONCLUSION: The significantly elevated asthma risk in subjects with a low copy number of the CCL3L1 gene which may be down-regulating IL-10 expression, not IL-6 expression.