Adrenomedullin suppresses tumour necrosis factor alpha-induced CXC chemokine ligand 10 production by human gingival fibroblasts

Authors

  • I. Hosokawa,

    1. Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, and
    Search for more papers by this author
  • Y. Hosokawa,

    Corresponding author
    1. Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, and
    Search for more papers by this author
  • K. Ozaki,

    1. Department of Oral Health Care Promotion, School of Oral Health and Welfare, Faculty of Dentistry, The University of Tokushima, Tokushima, Tokushima, Japan
    Search for more papers by this author
  • H. Nakae,

    1. Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, and
    Search for more papers by this author
  • T. Matsuo

    1. Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, and
    Search for more papers by this author

Dr Yoshitaka Hosokawa, Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, 770-8504, Japan.
E-mail: hosokawa@dent.tokushima-u.ac.jp

Summary

Periodontal disease is an inflammatory disorder characterized by the involvement of chemokines that are important for the recruitment of leucocytes. Several cytokines, including tumour necrosis factor alpha (TNF-α), are involved in regulating levels of chemokines in periodontal disease. CXC chemokine ligand 10 (CXCL10) is a chemokine related to the migration of T helper 1 cells. In this study, we examined CXCL10 expression in human gingival fibroblasts (HGFs). Moreover, we investigated the effects of adrenomedullin (AM), which is a multi-functional regulatory peptide, on the production of CXCL10 by HGFs. We revealed that TNF-α stimulation induced CXCL10 production by HGFs. HGFs expressed AM and AM receptors, calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP) 2, mRNAs constitutively. AM treatment supressed CXCL10 production by TNF-α-stimulated HGFs. Moreover, we elucidated that AM produced by HGFs inhibited CXCL10 production by HGFs, because AM antagonist enhanced CXCL10 production by HGFs. TNF-α treatment enhanced CRLR and RAMP2 mRNA expression in HGFs. Furthermore, AM is expressed in human periodontal tissues, including both inflamed and clinically healthy tissues. These results suggest that the CXCL10 produced by HGFs may be involved in the migration of leucocytes into inflamed tissues and related to exacerbation of periodontal disease. AM might be a therapeutic target of periodontal disease, because AM can inhibit CXCL10 production by HGFs.

Ancillary