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International Immunology 2007 19(9):1095-1102; doi:10.1093/intimm/dxm083
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© The Author 2007. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press and The Japanese Society for Immunology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org

CXCL16 is a novel mediator of the innate immunity of epidermal keratinocytes

Mikiko Tohyama1, Koji Sayama1, Hitoshi Komatsuzawa2, Yasushi Hanakawa1, Yuji Shirakata1, Xjuju Dai1, Lujun Yang1, Sho Tokumaru1, Hiroshi Nagai1, Satoshi Hirakawa1, Motoyuki Sugai2 and Koji Hashimoto1

1 Department of Dermatology, Ehime University School of Medicine, Shitsukawa, Toon-city, Ehime 791-0295, Japan
2 Department of Bacteriology, Hiroshima University Graduate School of Biomedicine, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan

Correspondence to: K. Sayama; E-mail: sayama{at}m.ehime-u.ac.jp

The epidermis is constantly exposed to a variety of microbial pathogens and plays a vital role in resisting them. Soluble CXC chemokine ligand (CXCL) 16, which is one of the ELR– CXC chemokines, acts as a mediator of innate immunity by attracting CXC chemokine receptor (CXCR) 6-expressing cells, such as activated T cells and NKT cells. However, the production of CXCL16 by non-immune cells remains unclear. We found that cultured keratinocytes produced a significant amount of CXCL16 (2–3 ng per 106 cells per 24 h). Stimulation with tumor necrosis factor {alpha}, IL-1{alpha}, IFN-{gamma}, peptidoglycan and polyinosinic-polycytidylic acid [poly(I:C)] enhanced CXCL16 production. The forms of CXCL16 in the culture supernatants had molecular weights of 14, 28 and 50 kDa. Immunohistochemical analysis revealed that the normal human epidermis expressed CXCL16. As several chemokines have anti-microbial activities, we studied the anti-microbial activity of CXCL16. The chemokine domain of CXCL16 at concentrations >5 µg ml–1 had significant anti-microbial activity against Staphylococcus aureus and Escherichia coli. Killing activity was retained at the physiological salt concentration in the presence of carbonate. In conclusion, CXCL16 is a novel mediator of the innate immune reactivities of epidermal keratinocytes.

Keywords: anti-microbial activity, chemokine, CXCL16, innate immunity, keratinocyte

Transmitting editor: T. Hirano

Received 13 December 2006, revised 23 May 2007, accepted 19 June 2007.


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