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Antimicrobial Agents and Chemotherapy, January 2007, p. 162-168, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00395-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The 6-Fluoro-8-Methoxy Quinolone Gatifloxacin Down-Regulates Interleukin-8 Production in Prostate Cell Line PC-3{triangledown}

Koh Takeyama,1,2 Hiroaki Mitsuzawa,1 Chiaki Nishitani,1 Takeyuki Shimizu,1 Hitomi Sano,1 Yasuharu Kunishima,2 Satoshi Takahashi,2 Hiroshi Hotta,2 Masanori Matsukawa,2 Ken-ichiro Shibata,3 Taiji Tsukamoto,2 and Yoshio Kuroki1*

Departments of Biochemistry,1 Urology, Sapporo Medical University School of Medicine, Sapporo, Japan,2 Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan3

Received 30 March 2006/ Returned for modification 23 July 2006/ Accepted 10 October 2006

Fluoroquinolones exhibit immunomodulatory effects on monocytes and macrophages, in addition to their bactericidal activities. It remains unknown even whether the quinolones act directly on the prostate. This study was based on the understanding of the molecular mechanisms of the actions of the fluoroquinolones that can be used for the treatment of chronic prostatitis/chronic pelvic pain syndrome. We investigated whether the 6-fluroro-8-methoxy quinolone gatifloxacin (GFLX) affected the production and secretion of interleukin-8 (IL-8) in the prostate cell line PC-3. GFLX decreased the level of IL-8 release from unstimulated PC-3 cells. GFLX also attenuated IL-8 secretion from PC-3 cells stimulated with peptidoglycan, Mycoplasma hominis, phorbol ester, and tumor necrosis factor alpha (TNF-{alpha}), indicating that GFLX exhibits an anti-inflammatory effect on the prostate cell line. However, GFLX failed to alter activation of the NF-{kappa}B and AP-1 elicited by these stimulants. GFLX significantly attenuated the expression of IL-8 mRNA in TNF-{alpha}-stimulated PC-3 cells and down-regulated the transcriptional activity of the 5'-flanking region of the IL-8 gene from –1481 to +44 bp. The deletion construct without the 5'-flanking region from –1481 to –170 bp but not the construct without the region from –1481 to –188 bp reversed the suppressive effect of GFLX on IL-8 promoter activity. These results demonstrate that GFLX suppresses IL-8 expression in the prostate cell line by decreasing the promoter activity of the IL-8 gene.

* Corresponding author. Mailing address: Department of Biochemistry, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo 060-8556, Japan. Phone: 81-11-611-2111, ext. 2670. Fax: 81-11-611-2236. E-mail: kurokiy{at}sapmed.ac.jp.

{triangledown} Published ahead of print on 16 October 2006.

Antimicrobial Agents and Chemotherapy, January 2007, p. 162-168, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00395-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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