title: IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells.
abstract: OBJECTIVE
  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 from human periodontal ligament cells (HPDLCs).
  
  
  METHODS
  CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs.
  
  
  RESULTS
  IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt) and signal transducer and activator of transcription (STAT)6 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 enhanced 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 to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions.
authors.affiliation: Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hosokawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Hosokawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Shindo
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuo
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054413:Chemokine CCL11 / Q000032:analysis / Q000378:metabolism*; D054418:Chemokine CCL20 / Q000032:analysis / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C544923:4-(benzylamino)-2-((2-(3-chloro-4-hydroxyphenyl)ethyl)amino)pyrimidine-5-carboxamide; C515456:CCL11 protein, human; C108355:CCL20 protein, human; D054413:Chemokine CCL11; D054418:Chemokine CCL20; D053583:Interleukin-1beta; D016328:NF-kappa B; D011743:Pyrimidines; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases