Two Sjogren syndrome-associated oral bacteria, Prevotella melaninogenica and Rothia mucilaginosa, induce the upregulation of major histocompatibility complex class I and hypoxia-associated cell death,

서지정보

ㆍ발행기관 : 대한구강생물학회 ㆍ수록지정보 : International Journal of Oral Biology / 46권 / 4호
ㆍ저자명 : Jaewon Lee, Sumin Jeon, Youngnim Choi

목차

Introduction
Materials and Methods
1. Cells
2. Bacteria
3. Immunofluorescence
4. Stimulation of HSG cells with TLR ligands orbacteria
5. Isolation of genomic DNA and removal ofendotoxins
6. TLR reporter cell assays
7. Flow cytometry
8. Cell Counting Kit-8 assay
9. Statistical analysis
Results
1. HSG cells express bacteria sensing TLRs andupregulate MHC I expression in response to theirligands
2. Pm and Rm activate TLR2 and TLR9 but not TLR4
3. Downregulation of MHC I expression by Rmcorrelates with bacterial invasion and cell death
4. Rm-induced cell death is not rescued by variouscell death inhibitors
5. Rm-induced cell death is associated with hypoxia
Discussion
References

영어 초록

Despite evidence that bacteria-sensing Toll-like receptors (TLRs) are activated in salivary gland tissues of Sjogren syndrome (SS) patients, the role of oral bacteria in SS etiopathogenesis is unclear. We previously reported that two SS-associated oral bacteria, Prevotella melaninogenica (Pm) and Rothia mucilagenosa (Rm), oppositely regulate the expression of major histocompatibility complex class I (MHC I) in human salivary gland (HSG) cells. Here, we elucidated the mechanisms underlying the differential regulation of MHC I expression by these bacteria. The ability of Pm and Rm to activate TLR2, TLR4, and TLR9 was examined using TLR reporter cells. HSG cells were stimulated by the TLR ligands, Pm, and Rm. The levels of MHC I expression, bacterial invasion, and viability of HSG cells were examined by flow cytometry. The hypoxic status of HSG cells was examined using Hypoxia Green. HSG cells upregulated MHC I expression in response to TLR2, TLR4, and TLR9 activation. Both Pm and Rm activated TLR2 and TLR9 but not TLR4. Rm-induced downregulation of MHC I strongly correlated with bacterial invasion and cell death. Rm-induced cell death was not rescued by inhibitors of the diverse cell death pathways but was associated with hypoxia. In conclusion, Pm upregulated MHC I likely through TLR2 and TLR9 activation, while Rm-induced hypoxia-associated cell death and the downregulation of MHC I, despite its ability to activate TLR2 and TLR9. These findings may provide new insight into how oral dysbiosis can contribute to salivary gland tissue damage in SS.

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