Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has previously been reported that, in periodontitis lesions, T cells with a memory/activated phenotype and with a type 2 cytokine profile accumulate in an oligoclonal fashion. Delineation of the role of cytokines in periodontal inflammation has, however, been complicated because of cross-regulation and because of their overlapping and often redundant effects. The aim of this study was to examine messenger RNA levels for interferon gamma, interleukin 4 (IL-4), IL-10, IL-12 and IL-13 in gingival tissues and peripheral blood mononuclear cells of patients with adult periodontitis. Reverse transcription polymerase chain reaction and subsequent image analysis was used to determine the level of mRNA for each cytokine. The mean expression of interferon gamma mRNA was significantly higher in peripheral blood mononuclear cells than in gingival tissues. In contrast, the mean expression of IL-10 mRNA was higher in gingival tissues than in peripheral blood mononuclear cells. This high expression of IL-10 mRNA was, in fact, seen in only 7 gingival tissue samples with the majority of samples showing levels similar to peripheral blood mononuclear cells. There was no difference in the mean expression of IL-12 p35 mRNA between gingival tissues and peripheral blood mononuclear cells. However, IL-12 p40 mRNA was expressed higher in gingival tissues than in peripheral blood mononuclear cells in 6 out of 16 samples with significant difference of mean expression. Like IL-10, gingival tissue samples and peripheral blood mononuclear cells expressed similar levels of IL-12 p40 mRNA. There was no difference in the mean expression of IL-13 in gingival tissues and peripheral blood mononuclear cells. Nevertheless, more peripheral blood mononuclear cell samples demonstrated high IL-13 mRNA expression than gingival tissue samples. IL-4 mRNA was weak but detectable in 3 gingival tissue samples. These results support the concept that cytokines form complex networks in periodontitis lesions and that their overlapping and redundant effects should be taken into account when considering the pathology of inflammatory periodontal disease. Dichotomous expression of IL-10 and IL-12 p40 mRNA in the periodontal lesion may be associated with disease entity.
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PMID:Cytokine messenger RNA expression in chronic inflammatory periodontal disease. 946 81

Porphyromonas gingivalis cysteine proteinases (gingipains) have been associated with virulence in destructive periodontitis, a disease process variously considered to represent an unregulated stimulation of either T helper type 1 (Th1)- or Th2-type cells. Critical in maintaining Th1 activity is the response of T lymphocytes to environmental interleukin 12 (IL-12) in the form of up-regulation of gamma interferon (IFN-gamma) production. Here we demonstrate that in the presence or absence of serum, gingipains were able to hydrolyze IL-12 and reduce the IL-12-induced IFN-gamma production from CD4+ T cells. However, the induction of IL-12 receptors on T cells by gingipains did not correlate with the enhancement of IFN-gamma production. The gingipains cleaved IL-12 within the COOH-terminal region of the p40 and p35 subunit chains, which leads to IL-12 inactivity, whereas IL-2 in these assays was not affected. Inactivation of IL-12 by the gingipains could disrupt the cytokine balance or favor Th2 activities in the progression of periodontitis.
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PMID:Hydrolysis of interleukin-12 by Porphyromonas gingivalis major cysteine proteinases may affect local gamma interferon accumulation and the Th1 or Th2 T-cell phenotype in periodontitis. 1150 Apr 41

The ability of certain pathogens to exploit innate immune function allows them to undermine immune clearance and thereby increase their persistence and capacity to cause disease. Porphyromonas gingivalis is a major pathogen in periodontal disease and is associated with increased risk of systemic conditions. We have previously shown that the fimbriae of P. gingivalis interact with complement receptor 3 (CR3; CD11b/CD18) in monocytes/macrophages, resulting in inhibition of IL-12p70 production in vitro. The in vivo biological implications of this observation were investigated in this study using a CR3 antagonist (XVA143). XVA143 was shown to block CR3 binding of P. gingivalis fimbriae and reverse IL-12p70 inhibition; specifically, CR3 blockade resulted in inhibition of ERK1/2 phosphorylation and up-regulation of IL-12 p35 and p40 mRNA expression. Importantly, mice pretreated with XVA143 elicited higher IL-12p70 and IFN-gamma levels in response to P. gingivalis i.p. infection and displayed enhanced pathogen clearance, compared with similarly infected controls. The notion that CR3 is associated with reduced IL-12p70 induction and impaired P. gingivalis clearance was confirmed using i.p. infected wild-type and CR3-deficient mice. Moreover, XVA143 dramatically attenuated the persistence and virulence of P. gingivalis in experimental mouse periodontitis, as evidenced by reduced induction of periodontal bone loss. Therefore, CR3 blockade may represent a promising immunomodulatory approach for controlling human periodontitis and possibly associated systemic diseases.
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PMID:Complement receptor 3 blockade promotes IL-12-mediated clearance of Porphyromonas gingivalis and negates its virulence in vivo. 1767 97