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Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis.
Nishida, Keigo; Hasegawa, Aiko; Yamasaki, Satoru; Uchida, Ryota; Ohashi, Wakana; Kurashima, Yosuke; Kunisawa, Jun; Kimura, Shunsuke; Iwanaga, Toshihiko; Watarai, Hiroshi; Hase, Koji; Ogura, Hideki; Nakayama, Manabu; Kashiwakura, Jun-Ichi; Okayama, Yoshimichi; Kubo, Masato; Ohara, Osamu; Kiyono, Hiroshi; Koseki, Haruhiko; Murakami, Masaaki; Hirano, Toshio.
Affiliation
  • Nishida K; Laboratory of Immune Regulation, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie, 513-8670, Japan. knishida@suzuka-u.ac.jp.
  • Hasegawa A; Laboratory for Homeostatic Network, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan. knishida@suzuka-u.ac.jp.
  • Yamasaki S; Laboratory for Homeostatic Network, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
  • Uchida R; Department of Pediatrics, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
  • Ohashi W; Laboratory for Homeostatic Network, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
  • Kurashima Y; Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
  • Kunisawa J; Laboratory of Immune Regulation, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagaki-cho, Suzuka, Mie, 513-8670, Japan.
  • Kimura S; Laboratory for Homeostatic Network, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi, Yokohama, Kanagawa, 230-0045, Japan.
  • Iwanaga T; Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, 930-0194, Japan.
  • Watarai H; Department of Innovative Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
  • Hase K; Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, the Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
  • Ogura H; Department of Mucosal Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
  • Nakayama M; Division of Clinical Vaccinology, International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
  • Kashiwakura JI; Institute for Global Prominent Research, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
  • Okayama Y; Chiba University-UC San Diego Center for Mucosal Immunology, Allergy and Vaccines (CU-UCSD cMAV), University of California San Diego, 9500 Gilman Dr. MC 0063, San Diego, CA, 92093-0063, United States.
  • Kubo M; Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Asagi Saito, Ibaraki, Osaka, 567-0085, Japan.
  • Ohara O; Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Asagi Saito, Ibaraki, Osaka, 567-0085, Japan.
  • Kiyono H; Division of Mucosal Vaccines, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
  • Koseki H; Laboratory of Histology and Cytology, Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan.
  • Murakami M; Division of Biochemistry, Faculty of Pharmacy, Keio University, Tokyo, 105-8512, Japan.
  • Hirano T; Laboratory of Histology and Cytology, Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638, Japan.
Sci Rep ; 9(1): 10842, 2019 07 25.
Article in En | MEDLINE | ID: mdl-31346193
ABSTRACT
Zinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Wound Healing / Interleukin-6 / Cation Transport Proteins / Receptors, G-Protein-Coupled / Mast Cells Limits: Animals Language: En Journal: Sci Rep Year: 2019 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Wound Healing / Interleukin-6 / Cation Transport Proteins / Receptors, G-Protein-Coupled / Mast Cells Limits: Animals Language: En Journal: Sci Rep Year: 2019 Document type: Article Affiliation country: