Periodontitis is an inflammatory disease against periodontal pathogen that results in loss of periodontal attachment and marginal alveolar bone destruction . It is character ized by infiltration of several immune cell types . S ubsets of CD4 T cells such as, T helper 1 (Th1), Th2, Th17 and T regulatory (Treg) cells have been found in diseased gingival tissues. Gingival fibroblasts (GFs) are predominant cell type in gingival conn ective tissue and it has been proven for being an essential regulatory function in the progression of periodontitis by
inflammatory response and extracellular matrix remodeling . The aim of this study was to evaluate whether GFs can be polarized into functi onal ly different subtypes by Th cytokines. Cultured human GFs were stimulated by 4 cytokines of Th1 (interferon gamma (IFN γ )), Th2 (interleukin 4 (IL 4)), Th17 (interleukin 17 (IL 17)) and regulatory T (transforming growth factor beta (TGF β )) cytokines. Messenger RNA expression profiling was analyzed by microarray. Several genes that appeared to be highly up or down regulat ed in the
microarray analysis were selected for reverse transcription polymerase chain reaction (RT-PCR). Up regulation and down regulation of genes on GFs by IFN γ was most prominent in absolute maximum fold change value and the number of expressed probes . The pattern of genetic expression on GFs by 4 Th cytokines (IFN-γ, IL-4, IL-17 or TGF-β) was shown functionally different. IFN-γ and IL-17 up-regulated genes related to inflammatory responses and extracellular matrix destruction whereas down-regulated genes related to anti-inflammatory responses and matrix synthesis. IL-4 promoted the expression of anti-inflammatory or tissue-reparative genes while suppressed inflammatory or tissue-destructive genes. TGF-β usually functioned like IL-4 up-regulating the expression of anti-inflammatory genes but also induced the expression of several inflammatory genes, such as pro-inflammatory cytokines. In conclusion, GFs can be polarized. In conclusion, GFs can be polarized into functionally different into functionally different subtypes by Th cytokines, and thus can function to promote or suppress inflammation and tissue destruction in gingival connective tissue.
