Basic ResearchExpression of Heat Shock Proteins in Periapical Granulomas
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Subjects and Samples
This study was approved by the Committee for Protection of Human Subjects at the University of Texas Health Science Center at Houston, Houston, TX. Subjects were patients (age, 15–57 years; average = 38.2 years) presenting with periapical lesions characterized radiographically as rarefaction lesions with the disappearance of the periodontal ligament space and discontinuity of the lamina dura; patients were referred for endodontic surgery when teeth failed to heal after conventional root canal
Gene Expression Analysis
The expression of all 44 HSP genes was significantly increased in the pool of periapical granulomas compared with the pool of healthy periodontal ligaments (P < .00001). DNAJC3, HSPA4, HSPA6, and HSPB1 showed the highest expression levels in the periapical granulomas (Fig. 2A). Similarly, the expression of HSP genes was significantly higher in LPS-treated macrophages in comparison with macrophages without LPS treatment (P < .0001), with DNAJC3, HSPA4, HSPA6, and HSPB1 being the most highly
Discussion
In this study, we hypothesized that HSPs could play a role in the development process of apical periodontitis and that macrophages could be a source of HSPs in this process. HSPs have numerous functions, including the facilitation of protein folding and antigen-presenting properties to the immune system 13, 14. Furthermore, extracellular HSPs can stimulate the release of TNF-α; IL-1β, -6 and -12; nitric oxide; and chemokines by monocytes/macrophages (15), which can contribute to the development
Acknowledgments
Supported in part by UTSD startup funds to R.M.S., AAE Foundation to S.C.G., Fundaçāo de Amparo a Pesquisa do Estado de Sāo Paulo (FAPESP) to G.P.G, and Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), BEX 1099/12-4, Brazil to L.C.S.
The authors thank the individuals that agreed to participate in this study and Pasha Goodman for invaluable help in the critical review of the manuscript.
The authors deny any conflicts of interest related to this study.
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Cited by (20)
Heat shock proteins in infection
2019, Clinica Chimica ActaCitation Excerpt :Interestingly, members of the HSP70 family were highly expressed in both periapical granulomas and LPS-treated macrophages. A positive correlation between HspA6/HspA7 and DNAJC3 with IL-6 mRNA levels, DNAJC3, HspA6/HspA7 and HspB1 with IL-1b mRNA levels, and DNAJC3 and HspB1 with RANKL and TNF-α mRNA levels was observed for major role of HSPs as immune response activators in inducing the host immune defense against pathogens [15]. As known, innate immunity is the first line of defense against pathogens and is necessary for survival of the infected host.
Role of HSP70 protein in human periodontal ligament cell function and physiology
2019, Annals of AnatomyCitation Excerpt :Yoshimatsu et al. reported on an enhanced expression of HSP47, which is actively involved in the regulation of collagen I synthesis, in the tension zone during orthodontic tooth movement (Yoshimatsu et al., 2008). Finally, a differential expression pattern of HSPs has been described in different endodontic periapical lesions (Goodman et al., 2014). However, information on the function of HSP in hPDL cell physiology, also in conditions requiring its inhibition for medical reasons, is still missing.
Proteomic Profiling and Differential Messenger RNA Expression Correlate HSP27 and Serpin Family B Member 1 to Apical Periodontitis Outcomes
2017, Journal of EndodonticsCitation Excerpt :Furthermore, the observed overexpression of the HSP27 protein in periapical granulomas is in line with our previously published findings in which HSP27 mRNA was significantly up-regulated in periapical granulomas and in lipopolysaccharide-stimulated macrophages (15). HSP27 expression was significantly higher in inactive lesions, implicating a potential role for this molecule in regulating lesion progression (15). Nevertheless, additional mechanistic studies are needed to determine a functional role for HSP27 in the pathogenesis of apical periodontitis.
Periapical Lesions Increase Macrophage Infiltration and Inflammatory Signaling in Muscle Tissue of Rats
2017, Journal of EndodonticsHeat Shock 70 Protein Genes and Genetic Susceptibility to Apical Periodontitis
2016, Journal of EndodonticsCitation Excerpt :Other studies have suggested that HSPA6 is a secondary regulator of stress at low expression levels, possibly depending on the cell type and growth conditions under non-stressed conditions (36). Members of the HSP70 gene family play a crucial role in the maintenance of infection and subsequent tissue destruction in autoimmune diseases and cancer (37), as well as in apical periodontitis (21). Furthermore, HSP70 proteins have known roles in the induction of proinflammatory cytokines and thereby may contribute to the pathogenesis of autoimmune disease and chronic inflammation (38).
Assessment of Apical Expression of Alpha-2 Integrin, Heat Shock Protein, and Proinflammatory and Immunoregulatory Cytokines in Response to Endodontic Infection
2015, Journal of EndodonticsCitation Excerpt :However, no data for ITGA2 were found in the literature. Hsp44 genes were significantly increased in a pool of periapical granulomas compared with a pool of healthy periodontal ligaments (19). These authors indicated that the HSP40 gene family plays a crucial role in the maintenance of infection and tissue destruction in apical periodontitis.