Comparative Analysis of ER Stress Activation Induced by Oral Bacteria
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Endoplasmic reticulum (ER) stress, caused by the accumulation of misfolded or unfolded proteins, activates the unfolded protein response to maintain cellular homeostasis and is implicated in bacterial infections. This study investigated ER stress activation in THP-1-derived macrophages infected with oral bacteria Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Streptococcus oralis at a multiplicity of infection of 50 for 4 hours. mRNA and protein expressions related to ER stress were analyzed by real-time polymerase chain reaction and Western blot, while pro-inflammatory cytokines were measured using enzyme-linked immunosorbent assay. P. gingivalis induced the highest mRNA expression of XBP1 and PERK, whereas A. actinomycetemcomitans showed elevated GRP78, ATF6, IRE1α, ATF4, and CHOP. P. intermedia strongly expressed PERK, while S. oralis showed higher GRP78, PERK, ATF4, and CHOP expression. Protein analysis revealed S. oralis had the highest phosphorylation levels of eIF2α and IRE1α, while CHOP was most highly expressed in P. intermedia. Pro-inflammatory cytokine expression showed P. intermedia and P. gingivalis elicited the most TNF-α, while P. gingivalis induced the highest IL-1β levels. These findings suggest oral bacteria induce varying levels of ER stress, influencing the progression of oral infectious diseases. Targeting ER stress could offer therapeutic potential for managing inflammatory conditions like periodontitis.
Abstract
Endoplasmic reticulum (ER) stress, caused by the accumulation of misfolded or unfolded proteins, activates the unfolded protein response to maintain cellular homeostasis and is implicated in bacterial infections. This study investigated ER stress activation in THP-1-derived macrophages infected with oral bacteria Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Streptococcus oralis at a multiplicity of infection of 50 for 4 hours. mRNA and protein expressions related to ER stress were analyzed by real-time polymerase chain reaction and Western blot, while pro-inflammatory cytokines were measured using enzyme-linked immunosorbent assay. P. gingivalis induced the highest mRNA expression of XBP1 and PERK, whereas A. actinomycetemcomitans showed elevated GRP78, ATF6, IRE1α, ATF4, and CHOP. P. intermedia strongly expressed PERK, while S. oralis showed higher GRP78, PERK, ATF4, and CHOP expression. Protein analysis revealed S. oralis had the highest phosphorylation levels of eIF2α and IRE1α, while CHOP was most highly expressed in P. intermedia. Pro-inflammatory cytokine expression showed P. intermedia and P. gingivalis elicited the most TNF-α, while P. gingivalis induced the highest IL-1β levels. These findings suggest oral bacteria induce varying levels of ER stress, influencing the progression of oral infectious diseases. Targeting ER stress could offer therapeutic potential for managing inflammatory conditions like periodontitis.
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