Severe skin inflammation leads to salivary gland atrophy and dysfunction

概要

Introduction
Saliva plays a role in digestion, taste, and normalization of the oral environment. Decreased salivation causes xerostomia and significantly impairs quality of life (QOL). We have previously investigated the systemic effects of severe long-lasting dermatitis on internal organs. We proposed a series of complications caused by skin-derived inflammatory cytokines as the concept of ”inflammatory skin march”.

Background
Psoriasis and atopic dermatitis are chronic systemic inflammatory skin diseases. It is known that these patients have symptoms localized to the skin as well as visceral complications. The prevalence of oral infections is significantly higher in these patients. However, the clear causal relationship between severe dermatitis and xerostomia remains unclear.

Objectives
This study aims to report the function and changes in salivary glands using a mouse spontaneous dermatitis model.

Methods
We used keratin 14-specific caspase-1 overexpressing transgenic (KCASPlTg) mice as spontaneous dermatitis model mice. In KCASPlTg mice, caspase-1, an enzyme that converts pro-IL-16 into the mature form of IL-16, is overexpressed in epidermal keratinocytes. The mice showed severe erosive dermatitis from 8 weeks of age. As a control group, littermate C57BL/6 (WT) mice were used. KCASPlTg and WT mice were stimulated with pilocarpine, and the induced saliva was collected. Histological analysis were also performed. The cytokine levels of the submandibular gland and saliva were determined using a panel kit with flow cytometer analysis.

Results
There was a significant difference in the amount of secreted saliva and the secretion ability between KCASPlTg and WT mice. In KCASPlTg mice, the secreted amount hardly increased even after stimulation. In histological analysis, KCASPlTg mice showed amyloid deposition and structure destruction in the submandibular gland. In cytokine analysis, an increase in inflammatory cytokines, such as IFN-y, IL-6, IL-12p70 and IL-23, in the lysate of submandibular gland of 20-week-old mice was observed in KCASPlTg mice compared to WT mice.

Discussion
In our study, salivary secretion was reduced in mice with systemic dermatitis. Amyloid deposition associated with systemic inflammation caused atrophy of salivary gland cells, resulted in fibrosis and the destruction of the glandular structure. The decrease in the secretion amount is because of the decrease in secretory ability owing to the destruction of the salivary glands. Decreased saliva secretion may cause dry mouth and periodontal disease.

Conclusion
Maintaining saliva secretion by suppressing skin inflammation may protect the oral environment and reduces the risk of inflammation loop, which result in the improving patients5 QOL.