Regulation of CXCL9/10/11 in oral keratinocytes and fibroblasts.
Th1 and Th2 cytokines such as interferon-gamma (IFN-gamma ) , tumor necrosis factor- alpha (TNF-alpha ), and IL-4 are expressed in T-cell-mediated inflammation in the oral cavity. We tested the hypothesis that those cytokines may act on CXCR3-agonistic chemokines, T-cell recruiting factors, and on neighboring cells, including oral keratinocytes and fibroblasts. Human immortalized oral keratinocytes (RT7) and fibroblasts (GT1) after 24-hour stimulation with IFN-gamma showed increased mRNA levels of CXCL9 (600- and 700-fold), CXCL10 (10,000- and 150-fold), and CXCL11 (5000- and 300-fold), respectively. In contrast, TNF-alpha caused an increase in CXCL9 (300-fold), CXCL10 (2000-fold), and CXCL11 (2000-fold) mRNA levels in GT1, but not RT7 cells, at 24 hrs. IL-4 reinforced the promotion of CXCL9, CXCL10, and CXCL11 expression by IFN-gamma in RT7 cells, whereas IL-4 inhibited the increased levels by IFN-gamma and TNF-alpha in GT1 cells. Thus, IFN-gamma , TNF-alpha , and IL-4 appear cooperatively to regulate CXCR3-agonistic chemokines in oral keratinocytes and fibroblasts in T-cell-mediated oral inflammation sites.
Ohta
K
K
Department of Oral and Maxillofacial Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Minami-Ku, Hiroshima 734-8553, Japan. otkouji@hiroshima-u.ac.jp
Shigeishi
H
H
Taki
M
M
Nishi
H
H
Higashikawa
K
K
Takechi
M
M
Kamata
N
N
D002460:Cell Line; D054357:Chemokine CXCL10 / Q000276:immunology*; D054371:Chemokine CXCL11 / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology*; D005881:Gingiva / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009061:Mouth Mucosa / Q000276:immunology* / Q000473:pathology; D054367:Receptors, CXCR3 / Q000819:agonists; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma