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Cytokines differentially regulate CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated human gingival fibroblasts. 2009

Y Hosokawa, and I Hosokawa, and K Ozaki, and H Nakae, and T Matsuo
Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

OBJECTIVE CXC chemokine 10 (CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T-helper 1 cells. In this study we examined the effects of cytokines on CXCL10 production by human gingival fibroblasts. METHODS Human gingival fibroblasts were exposed to pro-inflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha), a T-helper 1 cytokine (interferon-gamma), T-helper 2 cytokines (interleukin-4, interleukin-13), T-helper 17 cytokines (interleukin-17A, interleukin-22) and regulatory T-cell cytokines (interleukin-10, transforming growth factor-beta1) for 24 h. CXCL10 production by human gingival fibroblasts was examined by enzyme-linked immunosorbent assay. RESULTS Human gingival fibroblasts produced CXCL10 protein upon stimulation with interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma. Treatment of human gingival fibroblasts with interferon-gamma in combination with tumor necrosis factor-alpha or interleukin-1beta resulted in a synergistic production of CXCL10. However, interleukin-4 and interleukin-13 inhibited CXCL10 production by interferon-gamma-stimulated or tumor necrosis factor-alpha-stimulated-human gingival fibroblasts. On the other hand, interleukin-17A and interleukin-22 enhanced CXCL10 production by human gingival fibroblasts treated with interferon-gamma and inhibited CXCL10 production by tumor necrosis factor-alpha-stimulated human gingival fibroblasts. Furthermore, the anti-inflammatory cytokine, interleukin-10, inhibited CXCL10 production by both interferon-gamma- and tumor necrosis factor-alpha-stimulated human gingival fibroblasts, but transforming growth factor-beta1 enhanced interferon-gamma-mediated CXCL10 production by human gingival fibroblasts. CONCLUSIONS These results mean that the balance of cytokines in periodontally diseased tissue may be essential for the control of CXCL10 production by human gingival fibroblasts, and the production of CXCL10 might be important for the regulation of T-helper 1 cell infiltration in periodontally diseased tissue.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007378 Interleukins Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. Interleukin
D010518 Periodontitis Inflammation and loss of connective tissues supporting or surrounding the teeth. This may involve any part of the PERIODONTIUM. Periodontitis is currently classified by disease progression (CHRONIC PERIODONTITIS; AGGRESSIVE PERIODONTITIS) instead of age of onset. (From 1999 International Workshop for a Classification of Periodontal Diseases and Conditions, American Academy of Periodontology) Pericementitis,Pericementitides,Periodontitides
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005881 Gingiva Oral tissue surrounding and attached to TEETH. Gums,Interdental Papilla,Papilla, Interdental,Gum
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha

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