Cytokine responses of human gingival fibroblasts to Actinobacillus actinomycetemcomitans cytolethal distending toxin.

• Actinobacillus actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, and has the capacity to express a cytolethal distending toxin (Cdt). Gingival fibroblasts (GF) are resident cells of the periodontium, which can express several osteolytic cytokines. The aims of this study were a) to investigate the role of Cdt in A. actinomycetemcomitans-induced expression of osteolytic cytokines and their cognate receptors in GF and b) to determine if the previously demonstrated induction of receptor activator of NFkappaB ligand (RANKL) by A. actinomycetemcomitans is mediated by these pro-inflammatory cytokines or by prostaglandin E(2) (PGE(2)). A. actinomycetemcomitans clearly induced interleukin (IL)-6, IL-1beta, and to a minimal extent, tumor necrosis factor (TNF)-alpha mRNA expression. At the protein level, IL-6 but not IL-1beta or TNF-alpha expression was stimulated. The mRNA expression of the different receptor subtypes recognizing IL-6, IL-1beta and TNF-alpha was not affected. A cdt-knockout strain of A. actinomycetemcomitans had similar effects on cytokine and cytokine receptor mRNA expression, compared to its parental wild-type strain. Purified Cdt stimulated IL-6, but not IL-1beta or TNF-alpha protein biosynthesis. Antibodies neutralizing IL-6, IL-1 or TNF-alpha, and the PGE(2) synthesis inhibitor indomethacin, did not affect A. actinomycetemcomitans-induced RANKL expression. In conclusion, a) A. actinomycetemcomitans induces IL-6 production in GF by a mechanism largely independent of its Cdt and b) A. actinomycetemcomitans-induced RANKL expression in GF occurs independently of IL-1, IL-6, TNF-alpha, or PGE(2).

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Odontologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dentistry (hsv//eng)

Nyckelord

Actinobacillus actinomycetemcomitans

genetics

pathogenicity

Bacterial Toxins

toxicity

Carrier Proteins

drug effects

genetics

metabolism

Cytokines

drug effects

genetics

metabolism

Dinoprostone

metabolism

Fibroblasts

drug effects

immunology

Gene Expression Regulation

drug effects

Gingiva

drug effects

metabolism

microbiology

Humans

Indomethacin

pharmacology

Inflammation Mediators

immunology

metabolism

Interleukin 1 Receptor Antagonist Protein

Membrane Glycoproteins

drug effects

genetics

metabolism

Mutation

RANK Ligand

Receptor Activator of Nuclear Factor-kappa B

Receptors

Interleukin-1

drug effects

genetics

metabolism

Receptors

Interleukin-1 Type II

Receptors

Interleukin-6

drug effects

genetics

metabolism

Receptors

Tumor Necrosis Factor

Type I

drug effects

genetics

metabolism

Receptors

Tumor Necrosis Factor

Type II

drug effects

genetics

metabolism

Sialoglycoproteins

pharmacology

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