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. 2021 Jul-Aug;35(4):2099-2106.
doi: 10.21873/invivo.12479.

Role of S100A4 in the Pathogenesis of Human Periapical Granulomas

Takahito Tamura  1   2 , Taiki Miyata  1   2 , Keisuke Hatori  3   4 , Kazuma Himi  1 , Takeshi Nakamura  1   2 , Yurika Toyama  1   2 , Osamu Takeichi  1   4
Affiliations

Role of S100A4 in the Pathogenesis of Human Periapical Granulomas

Takahito Tamura et al. In Vivo. 2021 Jul-Aug.

Abstract

Background/aim: S100A4 expression is associated with the pathology of chronic inflammatory diseases. In this study, we investigated the role of S100A4 and four inflammatory mediators (IL-1β, IκB, IL-10, and TNF-α) in human periapical granulomas (PGs).

Materials and methods: S100A4 expression in PGs obtained by apicoectomy was examined by immunohistochemistry. Further, the expression of S100A4 and four inflammatory mediators was compared between PGs and healthy gingival tissues (HGTs) using real-time PCR.

Results: In the PGs, S100A4 was found to be expressed in endothelial cells and fibroblasts. Furthermore, real-time PCR revealed that the expression of S100A4 and IL-1β in PGs was significantly higher than that in HGTs. Although a correlation between the expression of S100A4 and IκB or IL-10 was not detected, a positive correlation between the expression of S100A4 and IL-1β or TNF-α was observed.

Conclusion: The expression of S100A4 correlates with the pathogenesis of PGs.

Keywords: Apical periodontitis; S100A4; endothelial cells; inflammatory mediators; periapical granulomas; real-time polymerase chain reaction.

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Conflict of interest statement

The Authors have no conflicts of interest to declare in relation to this study.

Figures

Figure 1
Figure 1. Histological examination of periapical lesions and healthy gingival tissues (HGTs) stained by haematoxylin and eosin (HE). (A) Periapical granulomas (PGs) exhibiting rich vasculature and inflammatory cell infiltration; (B) Radicular cysts (RCs) with epithelial cell lining; and (C) HGTs. Scale bars=100 μm.
Figure 2
Figure 2. Immunohistochemical analysis of PGs with human S100A4 antibody. (A) S100A4-positive endothelial cells, fibroblasts, and lymphocytes were observed in human periapical granulomas (PGs). Arrows indicate the cells expressing S100A4 (Scale bar=15 μm). (B) S100A4 expression was not detected in healthy gingival tissues (HGTs) (Scale bar=50 μm).
Figure 3
Figure 3. Real-time PCR analysis for S100A4, IL-1β, IĸB, IL-10, and TNF-α mRNA expression in periapical granulomas (PGs) and healthy gingival tissues (HGTs); mRNA expression was normalised to that of GAPDH mRNA expression. Horizontal black bars indicate the median. The expression levels of all mRNAs in HGTs were significantly lower than those in PGs. **p<0.01 (Mann-Whitney U-test).
Figure 4
Figure 4. Real-time PCR and Pearson’s correlation coefficient analysis were performed to compare the mRNA expression of S100A4 with that of IL-1β, IĸB, IL-10, and TNF-α in human periapical granulomas (PGs). (A, D) A positive correlation between the expression of S100A4 and IL-1β (p=0.0055, R2=0.2704) and that of S100A4 and TNF-α (p<0.001, R2=0.409) was noted. (B, C) A correlation between the expression of S100A4 and IĸB (p=0.8283, R2=0.0016) and that of S100A4 and IL-10 (p=0.2784, R2=0.0389) was not observed.
Figure 5
Figure 5. Potential role of S100A4 in periapical granulomas (PGs). (A) Inflammatory cells infiltrate and express IL-1β in PGs. (B) IL-1β induces S100A4 expression in inflammatory cells. (C) The expression of TNF-α stimulated by S100A4 upregulates the inflammatory response.
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