This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishikawa, C.
Right arrow Articles by Yamanishi, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishikawa, C.
Right arrow Articles by Yamanishi, K.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2009, p. 1760-1765, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01540-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Tetracyclines Modulate Protease-Activated Receptor 2-Mediated Proinflammatory Reactions in Epidermal Keratinocytes{triangledown}

Chika Ishikawa,{dagger} Tatsuya Tsuda,{dagger} Hiroe Konishi, Noboru Nakagawa, and Kiyofumi Yamanishi*

Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan

Received 19 November 2008/ Returned for modification 17 December 2008/ Accepted 16 February 2009

In addition to their antibiotic effects, tetracyclines have anti-inflammatory action that is often beneficial in the control of inflammatory skin disorders. In this study, we examined the effects of tetracycline (TET) and two of its derivatives, doxycycline (DOX) and minocycline (MIN), on the production of interleukin-8 (IL-8) elicited by the activation of protease-activated receptor 2 (PAR2) in normal human epidermal keratinocytes (NHEK). In NHEK, the production of IL-8 stimulated by an agonist peptide of PAR2, SLIGKIV-NH2, at 100 µM was significantly reduced by TET, DOX, or MIN at 5 and 10 µM, concentrations that are noncytotoxic. The tumor necrosis factor alpha (TNF-{alpha})-induced production of IL-8 was synergistically augmented by SLIGKIV-NH2, and that synergistic increase in the production of IL-8 was suppressed by 100 nM PAR2-specific small interfering RNA. It was also suppressed by TET, DOX, or MIN but not by the 14-membered-ring macrolide antibiotics erythromycin, roxithromycin, and clarithromycin, which also have anti-inflammatory activities, at 10 µM. These results suggest that tetracyclines attenuate the PAR2-IL-8 axis in keratinocytes and thereby effectively modulate proinflammatory responses in the skin.

* Corresponding author. Mailing address: Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. Phone: 81-798-45-6653. Fax: 81-798-45-6651. E-mail: kyamanis{at}hyo-med.ac.jp

{triangledown} Published ahead of print on 2 March 2009.

{dagger} C.I. and T.T. contributed equally to this work.

Antimicrobial Agents and Chemotherapy, May 2009, p. 1760-1765, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01540-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»