Candida albicans {beta}-Glucan-Containing Particles Increase HO-1 Expression in Oral Keratinocytes via a Reactive Oxygen Species/p38 Mitogen-Activated Protein Kinase/Nrf2 Pathway [Host Response and Inflammation]

Oral keratinocytes provide the first line of host defense against oral candidiasis. We speculated that interactions of fungal cell wall components with oral keratinocytes regulate the stress response against Candida infection and examined the expression of genes induced by heat-killed Candida albicans in oral immortalized keratinocytes using a cDNA microarray technique. Of 24,000 genes revealed by that analysis, we focused on HO-1, a stress-inducible gene, as its expression was increased by both heat-killed and live C. albicans. In histological findings, HO-1 expression in the superficial layers of the oral epithelium following Candida infection was elevated compared to that in healthy epithelium. We then investigated fungal cell wall components involved in induction of HO-1 expression and found that β-glucan-containing particles (β-GPs) increased its expression. Furthermore, β-glucan was observed on the surface of both heat-killed C. albicans and Candida cells that had invaded the oral epithelium. Fungal β-GPs also promoted induction of intracellular reactive oxygen species (ROS), NADPH oxidase activation, and p38 mitogen-activated protein kinase (MAPK) phosphorylation, while those specific inhibitors inhibited the HO-1 expression induced by fungal β-GPs. Moreover, fungal β-GPs induced Nrf2 translocation into nuclei via p38 MAPK signaling, while the HO-1 expression induced by fungal β-GPs was inhibited by Nrf2-specific small interfering RNA...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research