BACKGROUND AND OBJECTIVE: Host responses in periodontitis span a range of local and emigrating cell types and biomolecules. Accumulating evidence regarding the expression of this disease across the population suggests some component of genetic variation that controls onset and severity of disease, in concert with the qualitative and quantitative parameters of the oral microbiome at sites of disease. However, there remains little information regarding the capacity of accruing environmental stressors or modifiers over a lifespan at both the host genetic and microbial ecology levels to understand fully the population variation in disease. This study evaluated the impact of environmental lead exposure on the responses of oral epithelial cells to challenge with a model pathogenic oral biofilm. METHODS AND RESULTS: Using NanoString technology to quantify gene expression profiles of an array of 511 host response-associated genes in the epithelial cells, we identified an interesting primary panel of basal responses of the cells with numerous genes not previously considered as major response markers for epithelial cells, eg, interleukin (IL)-32, CTNNB1, CD59, MIF, CD44 and CD99. Even high levels of environment lead had little effect on these constitutive responses. Challenge of the cells with the biofilms (Streptococcus gordonii/Fusobacterium nucleatum/Porphyromonas gingivalis) resulted in significant increases in an array of host immune-related genes (134 of 511). The greatest magnitude in differential expression was observed with many genes not previously described as major response genes in epithelial cells, including IL-32, CD44, NFKBIA, CTSC, TNFAIP3, IL-1A, IL-1B, IL-8 and CCL20. The effects of environmental lead on responses to the biofilms were mixed, although levels of IL-8, CCL20 and CD70 were significantly decreased at lead concentrations of 1 and/or 5 μmol/L. CONCLUSION: The results provided new information on a portfolio of genes expressed by oral epithelial cells, targeted substantial increases in an array of immune-related genes post-biofilm challenge, and a focused impact of environmental lead on these induced responses.
BACKGROUND AND OBJECTIVE: Host responses in periodontitis span a range of local and emigrating cell types and biomolecules. Accumulating evidence regarding the expression of this disease across the population suggests some component of genetic variation that controls onset and severity of disease, in concert with the qualitative and quantitative parameters of the oral microbiome at sites of disease. However, there remains little information regarding the capacity of accruing environmental stressors or modifiers over a lifespan at both the host genetic and microbial ecology levels to understand fully the population variation in disease. This study evaluated the impact of environmental lead exposure on the responses of oral epithelial cells to challenge with a model pathogenic oral biofilm. METHODS AND RESULTS: Using NanoString technology to quantify gene expression profiles of an array of 511 host response-associated genes in the epithelial cells, we identified an interesting primary panel of basal responses of the cells with numerous genes not previously considered as major response markers for epithelial cells, eg, interleukin (IL)-32, CTNNB1, CD59, MIF, CD44 and CD99. Even high levels of environment lead had little effect on these constitutive responses. Challenge of the cells with the biofilms (Streptococcus gordonii/Fusobacterium nucleatum/Porphyromonas gingivalis) resulted in significant increases in an array of host immune-related genes (134 of 511). The greatest magnitude in differential expression was observed with many genes not previously described as major response genes in epithelial cells, including IL-32, CD44, NFKBIA, CTSC, TNFAIP3, IL-1A, IL-1B, IL-8 and CCL20. The effects of environmental lead on responses to the biofilms were mixed, although levels of IL-8, CCL20 and CD70 were significantly decreased at lead concentrations of 1 and/or 5 μmol/L. CONCLUSION: The results provided new information on a portfolio of genes expressed by oral epithelial cells, targeted substantial increases in an array of immune-related genes post-biofilm challenge, and a focused impact of environmental lead on these induced responses.
Authors: Octavio A Gonzalez; Sreenatha Kirakodu; Linh M Nguyen; Luis Orraca; Michael J Novak; Janis Gonzalez-Martinez; Jeffrey L Ebersole Journal: Front Oral Health Date: 2022-05-23