Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans

Uehara, Akiko; Sugawara, Shunji; Takada, Haruhiko

doi:10.1099/0022-1317-51-8-626

Cited by 97 publications

(80 citation statements)

References 51 publications

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“…TNF-␣, but not IFN-␥, induced IL-8 production from HGFs; these observations agree with those of previous studies (3,51,52). 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).…”

Section: Discussionmentioning

confidence: 99%

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

Mahanonda

Sa‐Ard‐Iam

Montreekachon

et al. 2007

The Journal of Immunology

131

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: 99%

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

Mahanonda

Sa‐Ard‐Iam

Montreekachon

et al. 2007

The Journal of Immunology

131

104

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“…Many reports have indicated that IL-12p40 production by DCs and macrophages (M/) was induced by stimulation with bacterial components through pattern-recognition receptors such as the toll-like receptors (TLRs) and the nucleotide-binding oligomerization domain (NOD) (Uehara et al 2002;Newton et al 2007). In particular, it has previously been reported that CpG-DNA is the main promoter of IL-12p40 (Albrecht et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Bifidobacterium components have immunomodulatory characteristics dependent on the method of preparation

et al. 2007

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Some bifidobacteria or lactobacilli exhibit a variety of immunomodulatory effects, such as being antiinflammatory, increasing IgA secretion, and moderating allergy. We prepared three types of Bifidobacterium components from B. pseudocatenulatum JCM 7041 (Bp) using preparation methods such as sonication, heat treatment, and non-treatment (live Bp). Furthermore, we compared their immunomodulatory effects using in vivo and in vitro immunological bio-assays. We determined immune responses such as cell proliferation and the production of cytokines and IgA in Peyer's patch cells in vitro following co-culture with bacterial components, and investigated the effects of oral administration of each of them on cytokine and IgA production by Peyer's patch cells. Live-, ultrasonic treated-and heat-treated Bp exhibited cytokineinducing and cell proliferation activities. Sonicated Bp in particular showed the greatest immunomodulatory activity in the short term as measured by in vitro and in vivo assays, while heat-treated Bp induced cytokines (e.g. IL-6 and IFN-c) and IgA production following oral administration for 7 consecutive days. These data showed that Bifidobacterium components prepared by different methods might induce different immune responses. Using scanning electron microscopy we demonstrated that the surface structure of sonicated Bp, which contained more soluble saccharides, was different from other components. These data suggest that the immunomodulatory effect of Bp is dependent upon the bacterial conformation and condition.

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“…TLR2 and -4 are expressed on oral epithelial cells and up-regulated with interferon gamma stimulation (Uehara et al, 2002b). The LPS binding factor, CD14, a cofactor in the association of bacterial LPS to TLR4, is poorly expressed on epithelial cells but is present in soluble form in plasma.…”

Section: Antimicrobial Peptides In the Oral Environment 123mentioning

confidence: 99%

“…Lipoteichoic acid and peptidoglycans of Gram positive organisms and LPS of Gram negative bacteria signal via TLR2 and TLR4, respectively, activating NF-κB transcription factors and the JNK pathways that mediate up-regulation of multiple innate and inflammatory responses. TLR2 and -4 are expressed on oral epithelial cells and up-regulated with interferon gamma stimulation (Uehara et al, 2002b). The LPS binding factor, CD14, a cofactor in the association of bacterial LPS to TLR4, is poorly expressed on epithelial cells but is present in soluble form in plasma.…”

Section: Epithelial Receptors For Hbd-2 Regulationmentioning

confidence: 99%

Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

2005

Current Issues in Molecular Biology

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The oral cavity is a unique environment in which antimicrobial peptides play a key role in maintaining health and may have future therapeutic applications. Present evidence suggests that α-defensins, β-defensins, LL-37, histatin, and other antimicrobial peptides and proteins have distinct but overlapping roles in maintaining oral health and preventing bacterial, fungal, and viral adherence and infection. The expression of the inducible hBD-2 in normal oral epithelium, in contrast to other epithelia, and the apparent differential signaling in response to commensal and pathogenic organisms, provides new insights into innate immunity in this body site. Commensal bacteria are excellent inducers of hBD-2 in oral epithelial cells, suggesting that the commensal bacterial community acts in a manner to benefit the overall innate immune readiness of oral epithelia. This may have major significance for understanding host defense in the complex oral environment. The oral environmentThe oral cavity is a unique environment. Oral mucosa is a critical protective interface between external and internal environments and must serve as a barrier to the myriad microbial species present in this warm, moist environment. The oral cavity is the only area of the body in which hard tissues break through the epithelial surface. The periodontal epithelium surrounding the tooth is specialized to form an attachment and seal around each tooth. This unique function imparts special challenges to the tissue and leads to certain vulnerabilities associated with periodontal disease, especially in view of the continual exposure to the bacterial biofilm (dental plaque) that forms on the tooth surface at the junction of the soft tissue. Thus, this anatomical region is one where there is a significant risk of bacterially induced infection and inflammation.Antimicrobial peptides are important contributors to maintaining the balance between health and disease in this complex environment. These include several salivary antimicrobial peptides, the β-defensins expressed in the epithelium, the α-defensins expressed in neutrophils, and the cathelicidin, LL-37, expressed in both epithelium and neutrophils. These peptides are part of the host innate immune response in this environment. Epithelia, polymorphonuclear leukocytes (neutrophils), and saliva all contribute to the maintaining the health of the oral cavity in overlapping but independent ways. This review will focus on the human oral cavity and include 1) the expression and function of antimicrobial peptides in the oral cavity in the context of innate immune responses, 2) regulation of β-defensins which has led to advances in our understanding of oral epithelial innate immunity, and 3) functional efficacy against oral microbes when it is known. Epithelial antimicrobial peptidesHistorically, the oral epithelium has been considered mainly as a passive covering that becomes damaged and ulcerated in disease. This view has changed dramatically and the epithelial compartment is now seen as providing both...

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Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans

Cited by 97 publications

References 51 publications

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

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

Bifidobacterium components have immunomodulatory characteristics dependent on the method of preparation

Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

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