Synthesis of proinflammatory cytokines by human gingival fibroblasts in response to lipopolysaccharides and interleukin‐1β

Agarwal, Sudha; Baran, Coşkun; Piesco, Nicholas P.; Quintero, J. C.; Langkamp, H.H.; Johns, Lee P.; Chandra, Charu S.

doi:10.1111/j.1600-0765.1995.tb01291.x

Cited by 106 publications

(81 citation statements)

References 27 publications

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“…Bacterial components of P. gingivalis, such as LPS, have also been demonstrated to have the ability to activate osteoclast formation indirectly by stimulating osteoclasts or inflammatory cells as a consequence of inducing inflammatory cytokines (9,30). Among inflammatory cytokines, IL-1 and TNF-␣ are thought to be pivotal factors in bone remodeling both in vitro and in vivo, and IL-6 has been observed in inflamed periodontal tissues (1,2,8,10,16,18). Diseased gingival tissue expressed high levels of IL-1, TNF-␣, and IL-1 receptor antagonist mRNA in the connective tissue compared to healthy gingival tissue (27,34).…”

Section: Discussionmentioning

confidence: 99%

Xylitol Inhibits Inflammatory Cytokine Expression Induced by Lipopolysaccharide fromPorphyromonas gingivalis

Han

Jeong

Nam

et al. 2005

Clin Vaccine Immunol

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Porphyromonas gingivalis is one of the suspected periodontopathic bacteria. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Inflammatory cytokines play important roles in the gingival tissue destruction that is a characteristic of periodontitis. Macrophages are prominent at chronic inflammatory sites and are considered to contribute to the pathogenesis of periodontitis. Xylitol stands out and is widely believed to possess anticaries properties. However, to date, little is known about the effect of xylitol on periodontitis. The aim of the present study was to determine tumor necrosis factor alpha (TNF-␣) and interleukin-1␤ (IL-1␤) expression when RAW 264.7 cells were stimulated with P. gingivalis LPS (hereafter, LPS refers to P. gingivalis LPS unless stated otherwise) and the effect of xylitol on the LPS-induced TNF-␣ and IL-1␤ expression. The kinetics of TNF-␣ and IL-1␤ levels in culture supernatant after LPS treatment showed peak values at 1 h (TNF-␣) and 2 to 4 h (IL-1␤), respectively. NF-B, a transcription factor, was also activated by LPS treatment. These cytokine expressions and NF-B activation were suppressed by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-B). Pretreatment with xylitol inhibited LPS-induced TNF-␣ and IL-1␤ gene expression and protein synthesis. LPS-induced mobilization of NF-B was also inhibited by pretreatment with xylitol in a dose-dependent manner. Xylitol also showed inhibitory effect on the growth of P. gingivalis. Taken together, these findings suggest that xylitol may have good clinical effect not only for caries but also for periodontitis by its inhibitory effect on the LPS-induced inflammatory cytokine expression.

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Section: Discussionmentioning

confidence: 99%

Xylitol Inhibits Inflammatory Cytokine Expression Induced by Lipopolysaccharide fromPorphyromonas gingivalis

Han

Jeong

Nam

et al. 2005

Clin Vaccine Immunol

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“…Three different concentrations of bacteria were used for the challenge (5 ϫ 10 7 , 5 ϫ 10 8 , and 5 ϫ 10 9 /ml), and all assessments were made in triplicate. Supernatants were collected at six different time points (1,3,6,12,24, and 48 h following challenge), centrifuged (13,000 ϫ g for 5 min), and frozen in multiple aliquots at Ϫ80°C. ELISA for cytokines.…”

Section: Methodsmentioning

confidence: 99%

Cytokine Responses toTreponema pectinovorumandTreponema denticolain Human Gingival Fibroblasts

Nixon¹,

Steffen

Ebersole

2000

Infect Immun

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Human gingival fibroblasts were challenged with Treponema pectinovorum and Treponema denticola to test three specific hypotheses: (i) these treponemes induce different cytokine profiles from the fibroblasts, (ii) differences in cytokine profiles are observed after challenge with live versus killed treponemes, and (iii) differences in cytokine profiles are noted from different gingival fibroblast cell lines when challenged with these treponemes. Three normal gingival fibroblast cell cultures were challenged with T. pectinovorum and T. denticola strains, and the supernatants were analyzed for cytokine production (i.e., interleukin-1␣ [IL-1␣], IL-1␤, IL-6, IL-8, IL-10, gamma interferon, macrophage chemotactic protein 1 [MCP-1], platelet-derived growth factor, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor). Unstimulated fibroblast cell lines produced IL-6, IL-8, and MCP-1. T. pectinovorum routinely elicited the greatest production of these cytokines from the fibroblast cell lines, increasing 10-to 50-fold over basal production. While T. denticola also induced IL-6 and IL-8 production, these levels were generally lower than those elicited by challenge with T. pectinovorum. MCP-1 levels were significantly lower after T. denticola challenge, and the kinetics suggested that this microorganism actually inhibited basal production by the fibroblasts. No basal or stimulated production of the other cytokines was observed. Significant differences were noted in the responsiveness of the various cell lines with respect to the two species of treponemes and the individual cytokines produced. Finally, dead T. pectinovorum generally induced a twofold-greater level of IL-6 and IL-8 than the live bacteria. These results supported the idea that different species of oral treponemes can elicit proinflammatory cytokine production by gingival cells and that this stimulation did not require live microorganisms. Importantly, a unique difference was noted in the ability of T. pectinovorum to induce a robust MCP-1 production, while T. denticola appeared to inhibit this activity of the fibroblasts. While the general cytokine profiles of the fibroblast cell cultures were similar, significant differences were noted in the quantity of individual cytokines produced, which could relate to individual patient variation in local inflammatory responses in the periodontium.

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“…For example, microbial factors such as LPS and cytokines such as IL-1 and TNF-␣induce IL-6 mRNA expression in fibroblasts (Agarwal et al, 1995). It has been reported that the effects of IL-1 and TNF-␣ are more involved in the regulation of IL-6 by fibroblasts rather than the direct effects of bacterial LPS (Kent et al, 1998).…”

Section: (2) Gingivalfibroblasts As Immunocompetent Cellsmentioning

confidence: 99%

Porphyromonas gingivalis Lipopolysaccharide Signaling in Gingival Fibroblasts–CD14 and Toll-like Receptors

Wang

Ohura

2002

Critical Reviews in Oral Biology & Medicine

223

200

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Periodontal disease is the major cause of adult tooth loss and is commonly characterized by a chronic inflammation caused by infection of oral bacteria. Porphyromonas gingivalis ( P. gingivalis ) is one of the suspected periodontopathic bacteria and is frequently isolated from the periodontal pockets of patients with chronic periodontal disease. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Gingival fibroblasts, which are the major constituents of gingival connective tissue, may directly interact with bacteria and bacterial products, including LPS, in periodontitis lesions. It is suggested that gingival fibroblasts play an important role in the host responses to LPS in periodontal disease. P. gingivalis LPS enhances the production of inflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor alpha (TNF-␣ ) in gingival fibroblasts. However, the receptor that binds with P. gingivalisLPS on gingival fibroblasts remained unknown for many years. Recently, it was demonstrated that P. gingivalis LPS binds to gingival fibroblasts. It was also found that gingival fibroblasts express CD14, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response gene 88 (MyD88). P. gingivalis LPS treatment of gingival fibroblasts activates several intracellular proteins, including protein tyrosine kinases, and up-regulates the expression of monocyte chemoattractant protein-1 (MCP-1), extracellular signal-regulated kinase 1 (ERK1), and signal-regulated kinase 2 (ERK2), IL-1 receptor-associated kinase (IRAK), nuclear factor-B (NF-B), and activating protein-1 (AP-1). These results suggest that the binding of P. gingivalis LPS to CD14 and TLR4 on gingival fibroblasts activates various second-messenger systems. In this article, we review recent findings on the signaling pathways induced by the binding of P. gingivalis LPS to CD14 and Toll-like receptors (TLRs) in gingival fibroblasts.

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Synthesis of proinflammatory cytokines by human gingival fibroblasts in response to lipopolysaccharides and interleukin‐1β

Cited by 106 publications

References 27 publications

Xylitol Inhibits Inflammatory Cytokine Expression Induced by Lipopolysaccharide fromPorphyromonas gingivalis

Xylitol Inhibits Inflammatory Cytokine Expression Induced by Lipopolysaccharide fromPorphyromonas gingivalis

Cytokine Responses toTreponema pectinovorumandTreponema denticolain Human Gingival Fibroblasts

Porphyromonas gingivalis Lipopolysaccharide Signaling in Gingival Fibroblasts–CD14 and Toll-like Receptors

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