International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Comparative analysis of endoplasmic reticulum stress activation induced by oral bacteria

  • Si Yeong Kim (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Jung Hwa Park (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Hee Sam Na (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Jin Chung (Department of Oral Microbiology, School of Dentistry, Pusan National University)
  • Received : 2024.10.24
  • Accepted : 2024.11.26
  • Published : 2024.12.31
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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 an 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.

Keywords

Acknowledgement

This work was supported by a 2-Year Research Grant of Pusan National University.

References

  1. Braakman I, Bulleid NJ. Protein folding and modification in the mammalian endoplasmic reticulum. Annu Rev Biochem 2011;80:71-99. doi: 10.1146/annurev-biochem-062209-093836
  2. Araki K, Nagata K. Protein folding and quality control in the ER. Cold Spring Harb Perspect Biol 2012;4:a015438. doi: 10.1101/cshperspect.a015438
  3. Díaz-Villanueva JF, Díaz-Molina R, García-González V. Protein folding and mechanisms of proteostasis. Int J Mol Sci 2015;16:17193-230. doi: 10.3390/ijms160817193
  4. Singh R, Kaur N, Dhingra N, Kaur T. Protein misfolding, ER stress and chaperones: an approach to develop chaperone based therapeutics for Alzheimer's disease. Int J Neurosci 2023;133:714-34. doi: 10.1080/00207454.2021.1968859
  5. Stefani IC, Wright D, Polizzi KM, Kontoravdi C. The role of ER stress-induced apoptosis in neurodegeneration. Curr Alzheimer Res 2012;9:373-87. doi: 10.2174/156720512800107618
  6. Hetz C, Saxena S. ER stress and the unfolded protein response in neurodegeneration. Nat Rev Neurol 2017;13:477-91. doi: 10.1038/nrneurol.2017.99
  7. Hosoi T, Ozawa K. Endoplasmic reticulum stress in disease: mechanisms and therapeutic opportunities. Clin Sci (Lond) 2009;118:19-29. doi: 10.1042/CS20080680
  8. Chandan K, Gupta M, Sarwat M. Role of host and pathogen-derived microRNAs in immune regulation during infectious and inflammatory diseases. Front Immunol 2020;10:3081. doi: 10.3389/fimmu.2019.03081
  9. Fioranelli M, Roccia MG, Flavin D, Cota L. Regulation of inflammatory reaction in health and disease. Int J Mol Sci 2021;22:5277. doi: 10.3390/ijms22105277
  10. Di Conza G, Ho PC. ER stress responses: an emerging modulator for innate immunity. Cells 2020;9:695. doi: 10.3390/cells9030695
  11. Celli J, Tsolis RM. Bacteria, the endoplasmic reticulum and the unfolded protein response: friends or foes? Nat Rev Microbiol 2015;13:71-82. doi: 10.1038/nrmicro3393
  12. Hasturk H, Kantarci A, Van Dyke TE. Oral inflammatory diseases and systemic inflammation: role of the macrophage. Front Immunol 2012;3:118. doi: 10.3389/fimmu.2012.00118
  13. DiRienzo JM. Breaking the gingival epithelial barrier: role of the Aggregatibacter actinomycetemcomitans cytolethal distending toxin in oral infectious disease. Cells 2014;3:476-99. doi: 10.3390/cells3020476
  14. Fu Y, Maaβ S, Cavallo FM, de Jong A, Raangs E, Westra J, Buist G, Becher D, van Dijl JM. Differential virulence of Aggregatibacter actinomycetemcomitans serotypes explained by exoproteome heterogeneity. Microbiol Spectr 2023;11:e0329822. doi: 10.1128/spectrum.03298-22
  15. Zhang S, Zhao Y, Lalsiamthara J, Peng Y, Qi L, Deng S, Wang Q. Current research progress on Prevotella intermedia and associated diseases. Crit Rev Microbiol 2024. doi: 10.1080/1040841X.2024.2390594. [Epub ahead of print]
  16. Yang I, Claussen H, Arthur RA, Hertzberg VS, Geurs N, Corwin EJ, Dunlop AL. Subgingival microbiome in pregnancy and a potential relationship to early term birth. Front Cell Infect Microbiol 2022;12:873683. doi: 10.3389/fcimb.2022.873683
  17. Sampaio-Maia B, Caldas IM, Pereira ML, Pérez-Mongiovi D, Araujo R. The oral microbiome in health and its implication in oral and systemic diseases. Adv Appl Microbiol 2016;97:171-210. doi: 10.1016/bs.aambs.2016.08.002
  18. Vila T, Sultan AS, Montelongo-Jauregui D, Jabra-Rizk MA. Oral candidiasis: a disease of opportunity. J Fungi (Basel) 2020;6:15. doi: 10.3390/jof6010015