Abstract
The human 60 kDa and microbial 65 kDa heat shock proteins (HSP) have been implicated in the pathogenesis of chronic periodontitis (CP) and coronary heart disease (CHD). We have studied 100 subjects: Group (a) consisted of patients with gingivitis (n = 25), group (b) were patients with CP (n = 25), group (c) patients with CHD and gingivitis (n = 25) and group (d) patients with CHD and CP (n = 25). PBMCs separated from peripheral blood were stimulated with medium, PMA/ionomycin, human HSP60, microbial HSP65, or no stimulus for 18 hours before intracellular IL-2, IFN-γ, TNF-α, IL-4, IL-5, or IL-17 were detected by flow cytometry. The mean fluorescence intensity (MFLI) for intracellular TNF-α was significantly increased when PBMC were stimulated with human HSP60 amongst the four groups (p = 0.001, ANOVA); pairwise comparisons revealed significant differences in MFLI between the gingivitis group and the CP (p = 0.017); between gingivitis and ging/CHD (p = 0.001) as well; but no significant difference between the CP and CP/CHD (p = 0.442). There was no significant difference in intracellular expression of IL-17, or any of the other cytokines tested; and the MFLI for HSP-stimulated were comparable to unstimulated cultures. When heat-labile human HSP60 was heated, intracellular cellular TNF-α expression was abrogated. In contrast, heat-stable LPS elicited TNF-α expression from monocytes in bulk cultures in all groups. These results suggest that the cytokine expression was dependent on human HSP60 and not LPS. Serum CRP was significantly associated with MFLI of intracellular TNF-α in CP patients (rs = 0.665, p = 0.026) and CP/CHD (rs = 0.699, p = 0.011). We conclude that human HSP60 elicits increased monocytic expression of TNF-α in patients with CP, CP/CHD or ging/CHD compared to patients with gingivitis. Since the marker of inflammation, namely CRP correlates with CP with or without CHD and not with mild chronic gingivitis or ging/CHD, this suggests that human HSP60-induced production of TNF-α is associated with CP and not CHD. There was no significant difference in intracellular expression of IL-17.
Highlights
Chronic periodontitis (CP) is an inflammatory disease characterised by connective tissue destruction and bone resorption, affecting 10% - 15% of the developed world population and is the major cause of tooth loss in adults [1]
Unstimulated cells incubated in medium showed relatively low mean fluorescence intensity (MFLI) (Figure 2(g)) in all intracellular cytokines studied; no statistically significant difference was found amongst the 4 groups (ANOVA, p = 0.803, Table 2)
There was a statistically significant difference amongst the 4 groups in MFLI for intracellular TNF-α by ANOVA (p = 0.001) (Table 2, Figures 2 and 3); between the gingivitis group compared to the CP group (p = 0.017) and between the gingivitis group and the ging/coronary heart disease (CHD)
Summary
Chronic periodontitis (CP) is an inflammatory disease characterised by connective tissue destruction and bone resorption, affecting 10% - 15% of the developed world population and is the major cause of tooth loss in adults [1]. The high degree of homology between microbial and human HSPs has led to the hypothesis that tissue damage can occur as a result of cross-reactivity between bacterial and human HSPs. Humoral and T cell responses to HSP60/65 have been demonstrated in CP [4,5,7,8,9]. In CP, there is controversy as to whether cells with a TH1 or TH2 cytokine profile are associated with disease progression, as both TH1 and TH2 cytokines are pro-
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