Endoplasmic Reticulum Stress in Periodontal Inflammation and Russell Body Presentation

Endoplasmic reticulum (ER) stress results in the activation of the unfolded protein response (UPR) pathways to alleviate stress and re-establish homeostasis. The UPR is composed of three axes (IRE1, ATF6 and PERK), which facilitate protein-folding, attenuate protein synthesis or induce apoptosis. The objectives of the current study were to examine the expression of genes crucial to the UPR pathways in inflamed periodontal tissues as compared to control tissues; and to determine which UPR genes were differentially expressed in inflamed periodontal tissue with and without Russell bodies (RB).

Methods:

Fourteen periodontal tissues were used. The tissues were histologically categorised into 3 groups: control (uninflamed/minimally inflamed), RB-ve (inflamed without RB) and RB+ve (inflamed with RB). Quantitative real-time reverse transcriptase polymerase chain reaction (qRT²-PCR) was performed for the analysis of gene expression.

Results:

A total of 84 genes related to the UPR pathways were analysed. A gene regulation threshold was set of >±2.0 fold-regulation and p<0.05. Genes down-regulated in association with periodontal inflammation as compared to control tissues were PPIA, GANC and heat shock proteins HSPA1B, HSPA2 and HSPA4. Comparison of inflamed RB+ve with the inflamed RB-ve groups found up-regulation of genes associated with protein translation (DNAJC3, SIL1), ER quality control (GANC, UGCGL1), ER-associated degradation (EDEM3) and an upstream transcription factor IRE1. 

Conclusions:

We have shown that heat shock proteins, an isomerase (PPIA) and an ER quality control component (GANC) were down-regulated in inflamed periodontal tissues. The negative regulation of heat shock proteins in relation to the host response in periodontal inflammation is of particular interest.  It was also shown that the expression of UPR genes differed based on the presence of RB. Interestingly IRE1 was the only upstream transcription factor that was induced. These genes may serve as markers of ER stress in inflamed tissues containing RB.

Funding: NZDA