IL-4 Modulates Chemokine Productions From IL-1β-stimulated Human Periodontal Ligament Cells

Objectives: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions in human periodontal ligament cells (HPDLCs).
Methods: HPDLCs were obtained from Lonza Walkersville Inc. CCL11 and CCL20 productions were measured with ELISA. Western blot analysis was used to detect Protein kinase B (Akt) and signal transducer and activator of transcription (STAT)6 phosphorylations in HPDLCs.
Results: IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 production from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that Akt and STAT6 pathways were highly activated in IL-4/IL-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β.
Conclusions: These results mean that IL-4 enhances Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues by inhibiting CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions. This work was supported by Grant-in-Aid for Scientific Research (C) (25463219) from Japan Society for the Promotion of Science.