DNA microarray analysis of human gingival fibroblasts from healthy and inflammatory gingival tissues

Wang, Pao-Li; Ohura, Kiyoshi; Fujii, Takeo; Oido-Mori, Mari; Kowashi, Yusuke; Kikuchi, Masanori; Suetsugu, Yasushi; Tanaka, Junzo

doi:10.1016/s0006-291x(03)00821-0

Cited by 134 publications

(120 citation statements)

References 15 publications

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“…Combinations of cytokines and bacterial PAMPs are known to modulate cytokine production from different cell types (53,54). A high level of IL-8 as well as the increased presence of IL-8-secreting fibroblasts has been detected in periodontitis lesions (6,55). Our data demonstrate that stimulation of HGFs with TNF-␣, combined with TLR ligands 2, 4, or 5, synergistically enhanced IL-8 production.…”

Section: Discussionmentioning

confidence: 60%

“…The kinetics study of IDO mRNA expression (6,12, and 24 h) was conducted using IFN-␥-or TNF-␣-treated HGFs. Twelve-hour-treated cells showed optimal mRNA expression of IDO.…”

Section: Mrna Expression Of Idomentioning

confidence: 99%

“…Cytokines IFN-␥, and TNF-␣ have been consistently detected in periodontitis lesions (6,7). We next investigated the effects on HGF production of IL-8 and IDO by either cytokine or by the combination of cytokine with different TLR ligands, specifically P. gingivalis LPS, poly(I:C), E. coli LPS, or S. typhimurium flagellin.…”

Section: Combination Of Tlr Ligand and Cytokine Stimulates Expressionmentioning

confidence: 99%

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IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

Mahanonda

Sa‐Ard‐Iam

Montreekachon

et al. 2007

The Journal of Immunology

132

104

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Human gingival fibroblasts (HGFs), a predominant cell type in tooth-supporting structure, are presently recognized for their active role in the innate immune response. They produce a variety of inflammatory cytokines in response to microbial components such as LPS from the key periodontal pathogen, Porphyromonas gingivalis. In this study, we demonstrated that HGFs expressed mRNA of TLRs 1, 2, 3, 4, 5, 6, and 9, but not TLRs 7, 8, and 10. Stimulation of HGFs with highly purified TLR2 ligand (P. gingivalis LPS), TLR3 ligand (poly(I:C)), TLR4 ligand (Escherichia coli LPS), and TLR5 ligand (Salmonella typhimurium flagellin) led to expression of IL-8 and IDO. A potent TLR 9 ligand, CpG oligodeoxynucleotide 2006 had no effect, although HGFs showed a detectable TLR9 mRNA expression. No significant enhancement on IL-8 or IDO expression was observed when HGFs were stimulated with various combinations of TLR ligands. Surprisingly, the TLR9 ligand CpG oligodeoxynucleotide 2006 was able to specifically inhibit poly(I:C)-induced IL-8 and IDO expression. TNF-α enhanced TLR ligand-induced IL-8 production in HGFs, whereas IFN-γ enhanced TLR ligand-induced IDO expression. HGF production of IDO in response to P. gingivalis LPS, IFN-γ, or the two in combination inhibited T cell proliferation in MLRs. The observed T cell inhibition could be reversed by addition of either 1-methyl-dl-tryptophan or l-tryptophan. Our results suggest an important role of HGFs not only in orchestrating the innate immune response, but also in dampening potentially harmful hyperactive inflammation in periodontal tissue.

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Section: Discussionmentioning

confidence: 60%

“…The kinetics study of IDO mRNA expression (6,12, and 24 h) was conducted using IFN-␥-or TNF-␣-treated HGFs. Twelve-hour-treated cells showed optimal mRNA expression of IDO.…”

Section: Mrna Expression Of Idomentioning

confidence: 99%

Section: Combination Of Tlr Ligand and Cytokine Stimulates Expressionmentioning

confidence: 99%

See 1 more Smart Citation

IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

Mahanonda

Sa‐Ard‐Iam

Montreekachon

et al. 2007

The Journal of Immunology

132

104

View full text Add to dashboard Cite

show abstract

“…Other types of inflammation, such as acute gingivitis caused by bacterial infiltration, can lead to constitutive upregulation of TLR2 and TLR4 in oral mucosa (26) with the epithelial layer providing the first line of defence against invading pathogens. Thus the expression of TLR3 exclusively in malignant cells is most likely not a remnant of defending persistent viral infections in the oral cavity but an additional mechanism of HNSCC contributing to the constitutive activity of NF-κB in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of c-Myc-dependent cell proliferation through toll-like receptor 3 in head and neck cancer

Pries¹,

Hogrefe²,

Xie³

et al. 2008

Int J Mol Med

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Abstract. Protein expression of human toll-like receptors (TLR) 1-10 was measured in cell lines and solid tumors of head and neck squamous cell carcinoma (HNSCC). All HNSCC cell lines and 80% of solid tumors were found to express TLR3 as a predominantly intracellular protein, while no other TLR proteins were expressed. TLR3 has previously been shown to contribute to the activation of nuclear factor-κB (NF-κB), a transcription factor which promotes several types of human cancers. Significantly, NF-κB expression was strongest in protein extracts from carcinoma tissue in which TLR3 was overexpressed. Inhibition of TLR3 expression in permanent HNSCC cell lines resulted in decreased expression of the oncoprotein c-Myc resulting in decreased cell proliferation. Correspondingly, overexpression of human TLR3 in mouse fibroblasts resulted in an upregulation of c-Myc and increased sensitivity for PolyI:C-induced cell proliferation. Our data suggest that TLR3 contributes to the malignant phenotype leading to invasive carcinoma in HNSCC.

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“…The DNA microarray technique provides a means to perform comprehensive expression analysis of a large number of pre-defined genes (12)(13)(14). In this study, we performed DNA microarray analysis to search for differentially expressed genes under the notion that they could provide diagnostic and therapeutic markers for pathogeneInt J Oral-Med Sci 12(1): [5][6][7][8][9][10][11][12]2013sis and lead to new treatments for IL-1β-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Microarray Analysis Detection of Signaling Pathway Responsive to IL-1β in Synovial Fibroblasts from TMJ

Kishida

Ogura

2013

Int J Oral-Med Sci

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Interleukin-1β (IL-1β) has important roles in the inflammation and connective tissue destruction observed in joint diseases such as rheumatoid arthritis. IL-1β is also a key mediator of intracapsular pathologic conditions of the temporomandibular joint (TMJ), including disk displacement/internal derangement and osteoarthritis. To identify putative IL-1β-responsive genes from arthritic disease tissues, gene expression of IL-1β treated and untreated synovial fibroblasts was measured using DNA microarray, and IL-1β-responsive genes were analyzed with GeneSpring. To measure the expression of 8,793 genes in synovial fibroblasts from five TMJ patients, significant changes between controls and IL-1β-treated cells (p < 0.05) were detected in 170 genes; 139 up-regulated genes, and 31 down-regulated genes. In addition, the biological interactions of IL-1β-regulated genes were investigated using Ingenuity Pathway Analysis, and it was found that IL-1β affects the expression of several genes in the NFκB signaling pathway. NFKB1 gene expression increased in synovial fibroblasts by IL-1β treatment. Gene expression of IKBa, TNFAIP3 and TNIP1, which are negative-feedback regulators, were also increased after IL-1β treatment in synovial fibroblasts. The increase in the expression of these genes was confirmed by real time-PCR analysis. The results suggest that IL-1β-responsive genes play important roles in the progression of inflammation and destruction of joint components.

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DNA microarray analysis of human gingival fibroblasts from healthy and inflammatory gingival tissues

Cited by 134 publications

References 15 publications

IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

IL-8 and IDO Expression by Human Gingival Fibroblasts via TLRs

Induction of c-Myc-dependent cell proliferation through toll-like receptor 3 in head and neck cancer

Microarray Analysis Detection of Signaling Pathway Responsive to IL-1β in Synovial Fibroblasts from TMJ

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