Laboratory of Veterinary Anatomy, Nippon Veterinary and Animal Science University, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan.
Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
J Oral Biosci. 2023 Sep;65(3):243-252. doi: 10.1016/j.job.2023.06.002. Epub 2023 Jun 19.
Histidine decarboxylase (HDC), a histamine synthase, is expressed in various tissues and is induced by proinflammatory cytokines such as TNFα. As they age, C57BL/6 mice show auto-antibody deposition and lymphocyte infiltration into various tissues, including salivary glands. However, the mechanism underlying cell infiltration and the change in HDC expression in salivary glands with aging remain unclear. Thus, we aimed to elucidate the relationship between histamine and inflammaging.
We investigated the change in histology and HDC expression in the major salivary glands (parotid, submandibular, and sublingual) of 6-week- and 9-month-old wild-type mice. We also determined the histological changes, cytokine expression, and anti-aging factor Klotho in the salivary glands of 9-month-old wild-type and HDC-deficient (HDC-KO) mice.
Cell infiltration was observed in the submandibular gland of 9-month-old wild-type mice. Although most cells infiltrating the submandibular glands were CD3-positive and B220-positive lymphocytes, CD11c-positive and F4/80-positive monocyte lineages were also detected. HDC, TNFα, and IL-1β mRNA expression increased in the submandibular gland of 9-month-old wild-type mice. The expression of PPARγ, an anti-inflammatory protein, declined in 9-month-old wild-type mice, and Klotho expression increased in 9-month-old HDC-KO mice. Immunohistochemistry showed that Klotho-positive cells disappeared in the submandibular gland of 9-month-old wild-type mice, while Klotho was detected in all salivary glands in HDC-KO mice of the same age.
Our findings demonstrate the multifunctionality of histamine and can aid in the development of novel therapeutic methods for inflammatory diseases such as Sjogren's syndrome and age-related dysfunctions.
组氨酸脱羧酶（HDC）是一种组氨酸合成酶，存在于多种组织中，并受 TNFα 等促炎细胞因子诱导。随着年龄的增长，C57BL/6 小鼠表现出自身抗体沉积和淋巴细胞浸润到各种组织，包括唾液腺。然而，衰老过程中唾液腺细胞浸润和 HDC 表达变化的机制尚不清楚。因此，我们旨在阐明组胺与炎症衰老之间的关系。
我们研究了 6 周龄和 9 月龄野生型小鼠主要唾液腺（腮腺、颌下腺和舌下腺）的组织学变化和 HDC 表达。我们还检测了 9 月龄野生型和 HDC 缺陷（HDC-KO）小鼠唾液腺的组织学变化、细胞因子表达和抗衰老因子 Klotho。
9 月龄野生型小鼠颌下腺可见细胞浸润。虽然浸润颌下腺的大多数细胞为 CD3 阳性和 B220 阳性淋巴细胞，但也检测到 CD11c 阳性和 F4/80 阳性单核细胞谱系。9 月龄野生型小鼠颌下腺 HDC、TNFα 和 IL-1β mRNA 表达增加。9 月龄野生型小鼠抗炎蛋白 PPARγ 表达下降，HDC-KO 小鼠 Klotho 表达增加。免疫组织化学显示，9 月龄野生型小鼠颌下腺 Klotho 阳性细胞消失，而同一年龄的 HDC-KO 小鼠所有唾液腺均检测到 Klotho。
我们的研究结果表明组胺具有多功能性，有助于开发治疗 Sjogren 综合征和与年龄相关功能障碍等炎症性疾病的新方法。
