Ecological DentistryOral Molecular Bioregulation

It is rare for diseases of the mouth (oral diseases) to produce life-threatening symptoms. However, oral diseases do cause a considerable drop in quality of life (QOL). Additionally, it is characteristic for systemic diseases to produce symptoms in the mouth and for oral diseases to produce symptoms throughout the body. Our laboratory works day and night to uncover the "mysteries" of our body system and diseases development by using immunology, molecular biology, and pharmacology. We then use this foundational research to take the first steps toward developing safe and effective prevention and treatment methods.

Our laboratory is composed not only of graduates from the school of dentistry but a staff of diverse backgrounds to seriously wrestle with our research. We openly welcome graduate students with an interest in the "mysteries" of life science, including those in dentistry. We are accepting many graduate students from clinical fields aspiring towards foundational research.


Topics of Research

  • Immunoregulation in the oral mucosa
  • Molecular mechanisms of salivary gland diseases
  • Role of chronic allergic inflammation in oral infectious diseases
  • Role of epithelial barrier dysfunction in oral infectious diseases
  • Regulation of oral mucosal homeostasis by oral commensal bacteria
  • Innate immune responses of bacterial cellular components
  • Pathological mechanisms of metal allergies
  • Immunological and inflammatory functions of biotin
  • Immunological and physiological functions of histamine

Recent Publications

  1. Kaji T, Kuroishi T, Bando K, Takahashi M, Sugawara S. N-acetyl cysteine inhibits IL-1α release from murine keratinocytes induced by 2-hydroxyethyl methacrylate. J Toxicol Sci. 2023; 48: 557-569.
  2. Tada H, Nishioka T, Ishiyama R, Song L, Onoue S, Kawahara K, Nemoto E, Matsushita K, Sugawara S. Macrophage migration inhibitory factor-mediated mast cell extracellular traps induce inflammatory responses upon Fusobacterium nucleatum infection. Biochem Biophys Res Commun. 2023; 674: 90-96.
  3. Tada H, Kawahara K, Osawa H, Song L, Numazaki K, Kawai J, Onoue S, Nishioka T, Nemoto E, Matsushita K, Sugawara S. Hericium erinaceus ethanol extract and ergosterol exert anti-inflammatory activities by neutralizing lipopolysaccharide-induced pro-inflammatory cytokine production in human monocytes. Biochem Biophys Res Commun. 2022; 636: 1-9.
  4. Lu L, Kuroishi T, Tanaka Y, Furukawa M, Nochi T, Sugawara S. Differential expression of CD11c defines two types of tissue-resident macrophages with different origins in steady-state salivary glands. Sci Rep. 2022; 12: 931. doi: 10.1038/s41598-022-04941-5. PMID: 35042931.
  5. Song L, Tada H, Nishioka T, Nemoto E, Imamura T, Potempa J, Li CY, Matsushita K, Sugawara S. Porphyromonas gingivalis gingipains-mediated degradation of plasminogen activator inhibitor-1 leads to delayed wound healing responses in human endothelial cells. J Innate Immun. 2021; 25: 1-14. doi: 10.1159/000519737. PMID: 34823251.
  6. Shishido K, Kuroishi T, Sugawara S. P2 purinergic receptor signaling and interleukin-1 synergistically induce interleukin-6 production in a human oral squamous carcinoma cell line. J Oral Biosci. 2021; 63: 80-90. doi: 10.1016/j.job.2021.01.004. PMID: 33497843.
  7. Kuroishi T, Bando K, Bakti RK, Ouchi G, Tanaka Y, Sugawara S. Migratory dendritic cells in skin-draining lymph nodes have nickel-binding capabilities. Sci Rep. 2020; 10: 5050. doi: 10.1038/s41598-020-61875-6. PMID: 32193426; PMCID: PMC7081353.
  8. Kuroishi T, Sugawara S. Metabolomic analysis of liver from dietary biotin deficient mice. J Nutr Sci Vitaminol (Tokyo). 2020; 66: 82-85. doi: 10.3177/jnsv.66.82. PMID: 32115458.
  9. Bando K, Kuroishi T, Sugawara S, Endo Y. Interleukin-1 and histamine are essential for inducing nickel allergy in mice. Clin Exp Allergy. 2019; 49: 1362-1373. doi: 10.1111/cea.13467. PMID: 31325186.
  10. Tanaka Y, Fukumoto S, Sugawara S. Mechanisms underlying the induction of regulatory T cells by sublingual immunotherapy. J Oral Biosci. 2019; 61: 73-77. doi: 10.1016/j.job.2019.02.001. PMID: 31109864.
  11. Tada H, Nishioka T, Takase A, Numazaki K, Bando K, Matsushita K. Porphyromonas gingivalis induces the production of interleukin-31 by human mast cells, resulting in dysfunction of the gingival epithelial barrier. Cell Microbiol. 2019; 21: e12972. doi: 10.1111/cmi.12972. PMID: 30423602.
  12. Kuroishi T, Bando K, Tanaka Y, Shishido K, Kinbara M, Ogawa T, Muramoto K, Endo Y, Sugawara S. CXCL4 is a novel nickel-binding protein and augments nickel allergy. Clin Exp Allergy. 2017; 47: 1069-1078. doi: 10.1111/cea.12926. PMID: 28319310.
  13. Bando K, Tanaka Y, Kuroishi T, Sasaki K, Takano-Yamamoto T, Sugawara S, Endo Y. Mouse model of hydroquinone hypersensitivity via innate and acquired immunity and its promotion by combined reagents. J Invest Dermatol. 2017; 137: 1082-1093. doi: 10.1016/j.jid.2016.12.018. PMID: 28108299.
  14. Tada H, Suzuki R, Nemoto E, Shimauchi H, Matsushita K, Takada H. Increases in IL-33 production by fimbriae and lipopeptide from Porphyromonas gingivalis in mouse bone marrow-derived dendritic cells via Toll-like receptor 2. Biomed Res. 2017; 38: 189-195. doi: 10.2220/biomedres.38.189. PMID: 28637954.
  15. Tada H, Shimizu T, Matsushita K, Takada H. Porphyromonas gingivalis-induced IL-33 down-regulates hCAP-18/LL-37 production in human gingival epithelial cells. Biomed Res. 2017; 38: 167-173. doi: 10.2220/biomedres.38.167. PMID: 28637951.
  16. Lu L, Tanaka Y, Ishii N, Sasano T, Sugawara S. CD103+CD11b- salivary gland dendritic cells have antigen cross-presenting capacity. Eur J Immunol. 2017; 47: 305-313. doi: 10.1002/eji.201646631. PMID: 27861804.
  17. Kinbara M, Bando K, Shiraishi D, Kuroishi T, Nagai Y, Ohtsu H, Takano-Yamamoto T, Sugawara S, Endo Y. Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice. Exp Dermatol. 2016; 25: 466-71. doi: 10.1111/exd.12985. PMID: 26910392.
  18. Tanaka Y, Nagashima H, Bando K, Lu L, Ozaki A, Morita Y, Fukumoto S, Ishii N, Sugawara S. Oral CD103-CD11b+ classical dendritic cells present sublingual antigen and induce Foxp3+ regulatory T cells in draining lymph nodes. Mucosal Immunol. 2017; 10: 79-90. doi: 10.1038/mi.2016.46. PMID: 27166558.
  19. Tada H, Matsuyama T, Nishioka T, Hagiwara M, Kiyoura Y, Shimauchi H, Matsushita K. Porphyromonas gingivalis gingipain-dependently enhances IL-33 production in human gingival epithelial cells. PLoS One. 2016; 11: e0152794. doi: 10.1371/journal.pone.0152794. PMID: 27058037; PMCID: PMC4825981.
  20. Tada H, Shimizu T, Nagaoka I, Takada H. Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells. Biomed Res. 2016; 37: 199-205. doi: 10.2220/biomedres.37.199. PMID: 27356607.
  21. Kuroishi T. Regulation of immunological and inflammatory functions by biotin. Can J Physiol Pharmacol. 2015; 93: 1091-6. doi: 10.1139/cjpp-2014-0460. PMID: 26168302.
  22. Nagai Y, Shiraishi D, Tanaka Y, Nagasawa Y, Ohwada S, Shimauchi H, Aso H, Endo Y, Sugawara S. Transportation of sublingual antigens across sublingual ductal epithelial cells to the ductal antigen-presenting cells in mice. Clin Exp Allergy. 2015; 45: 677-86. doi: 10.1111/cea.12329. PMID: 24773115.
  23. Bando K, Takahashi H, Kinbara M, Tanaka Y, Kuroishi T, Sasaki K, Takano-Yamamoto T, Sugawara S, Endo Y. Resin monomers act as adjuvants in Ni-induced allergic dermatitis in vivo. J Dent Res. 2014; 93: 1101-7. doi: 10.1177/0022034514552674. PMID: 25252875; PMCID: PMC4293772.
  24. Kuroishi T, Bando K, Endo Y, Sugawara S. Metal allergens induce nitric oxide production by mouse dermal fibroblasts via the hypoxia-inducible factor-2α-dependent pathway. Toxicol Sci. 2013; 135: 119-28. doi: 10.1093/toxsci/kft142. PMID: 23788631.

Laboratory Contacts

Senior Assist. Prof. Toshinobu Kuroishi