Activation pattern of neutrophils from blood of elderly individuals with Candida-related denture stomatitis.

We have identified impaired neutrophils in elderly individuals which could be involved with Candida-related denture stomatitis (DS), an oral infection predominantly caused by Candida albicans, affecting especially elderly individuals using dental prosthesis. However, specific mechanisms performed by neutrophil contributing to the susceptibility of the elderly to DS are not fully understood. This study evaluated activation features of blood neutrophils from elderly and young individuals with DS. Blood neutrophils cultured with C. albicans from elderly subjects secreted decreased levels of CXCL8. However, C. albicans challenged-neutrophils from DS patients produced high IL-4 and IL-10, and low GM-CSF levels, regardless of age. Additional elastase activity of neutrophils from both elderly groups was detected after incubation with C. albicans, but only neutrophils from elderly DS demonstrated high myeloperoxidase activity. Therefore, DS patients have affected neutrophils, and the advance of age intensifies these damages. In summary, individuals with Candida-related denture stomatitis presented variation in the neutrophil phenotype and activation. Such alterations were more intense in neutrophils from infected elderly individuals.

Characterization of a novel oral glucocorticoid system and its possible role in disease.

Synthetic corticosteroids are used widely for the treatment of a variety of diseases of the mouth. However, little is known as to whether the oral mucosa is able to modulate the local concentration of active corticosteroids or to produce steroids de novo. This has important clinical implications, because tissue-specific regulation of glucocorticoids is a key determinant of the clinical efficacy of these drugs. In the present study, we show that oral fibroblasts and keratinocytes expressed ACTH receptor (MC2R), glucocorticoid receptor (GR), and 11ß-hydroxysteroid dehydrogenases (11ß-HSDs). Unlike keratinocytes, fibroblasts lacked 11ß-HSD2 and could not effectively deactivate exogenously administered cortisol. However, both cell types were able not only to activate cortisone into the active form cortisol, but also to synthesize cortisol de novo following stimulation with ACTH. 11ß-HSD2, the enzyme controlling cortisol deactivation, exhibited different patterns of expression in normal (squamous epithelium and salivary glands) and diseased oral mucosa (squamous cell carcinoma and mucoepidermoid carcinoma). Blocking of endogenous cortisol catabolism in keratinocytes with the 11ß-HSD2 inhibitor 18ß-glycyrrhetinic acid mimicked the effect of exogenous administration of hydrocortisone and partially prevented the detrimental effects induced by pemphigus vulgaris sera. Analysis of the data demonstrates that a novel, non-adrenal glucocorticoid system is present in the oral mucosa that may play an important role in disease.

Differences between salivary and blood neutrophils from elderly and young denture wearers.

We previously showed that neutrophils from patients with Candida-related denture stomatitis exhibited damaged function, and the advance in age intensified this condition. Because such alterations had been determined in elderly people that were not denture wearers, the purpose of this study was to clarify functional and phenotypic characteristics of neutrophils from elderly denture wearers (EDW) and young denture wearers (YDW) without oral lesion. We enrolled 20 denture wearers (12 EDW and 8 YDW) and determined the positivity of Candida species on maxillary prosthesis and palate. Additionally, blood and salivary neutrophils were evaluated. Furthermore, cytokines and chemokines salivary levels were detected. YDW presented higher positivity of Candida albicans than elderly ones. However, blood neutrophils from EDW expressed less CXCR1, CD62L and CD11b and had lower C. albicans phagocytosis than YDW. Although myeloperoxidase and elastase activity was significantly higher in C. albicans-stimulated blood neutrophils from elderly, they produced high levels of IL-10 and low levels of Granulocyte macrophage-colony stimulating factor (GM-CSF). Despite apoptosis rate of salivary neutrophils was enhanced, these cells were at a high number in YDW. GM-CSF and IL10 were lower in saliva from elderly group. These data confirmed that ageing affects blood and salivary neutrophils and could predispose elderly to persistent oral infections.