Histamine deficiency inhibits lymphocyte infiltration in the submandibular gland of aged mice via increased anti-aging factor Klotho |
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| Affiliation: | 1. Laboratory of Veterinary Anatomy, Nippon Veterinary and Animal Science University, 1–7–1 Kyonan-cho, Musashino-shi, Tokyo, 180–8602, Japan;2. Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan;1. Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Faculty of Dental Medicine, Hokkaido University, Sapporo, Japan;2. Central Research Institute, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan;3. Northern Army Medical Unit, Camp Makomanai, Japan Ground Self-Defense Forces, Sapporo, Japan;4. Division of Craniofacial Development and Tissue Biology, Tohoku University Graduate School of Dentistry, Sendai, Japan;5. Orthopedics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan;6. Shandong Provincial Key Laboratory of Oral Biomedicine, The School of Stomatology, Shandong University, Jinan, China;1. University Medical Center Göttingen, Department of Medical Ethics and History of Medicine, Humboldtallee 36, 37073 Göttingen, Germany;2. University of Erlangen-Nürnberg, Department of Sociology, Kochstraße 4, 91054 Erlangen, Germany;1. Departments of Surgery, University of Colorado Denver, Aurora, CO 80045, USA;2. Division of Cardiology, the First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China;3. Departments of Medicine, University of Colorado Denver, Aurora, CO 80045, USA;1. Institute of Materia Medica, Shandong Academy of Medical Sciences, Key Laboratory for Biotech-Drugs Ministry of Health, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Jinan 250062, China;2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;3. Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012, China;1. Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China;2. Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China;3. The Second Affiliated Hospital of Jinzhou Medical University, Jinzhou, China;4. Department of Oral and Maxillofacial Surgery, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China;1. Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran;2. Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish, Iran;3. Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Box: 771664-8798, Rafsanjan, Iran;4. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran |
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| Abstract: | ObjectivesHistidine 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.MethodsWe 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.ResultsCell 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.ConclusionOur 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. |
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