The 6-fluoro-8-methoxy quinolone gatifloxacin down-regulates interleukin-8 production in prostate cell line PC-3.
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-kappaB 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.
Takeyama
Koh
K
Department of Biochemistry, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-Ku, Sapporo 060-8556, Japan.
Mitsuzawa
Hiroaki
H
Nishitani
Chiaki
C
Shimizu
Takeyuki
T
Sano
Hitomi
H
Kunishima
Yasuharu
Y
Takahashi
Satoshi
S
Hotta
Hiroshi
H
Matsukawa
Masanori
M
Shibata
Ken-Ichiro
K
Tsukamoto
Taiji
T
Kuroki
Yoshio
Y
D000890:Anti-Infective Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology*; D000077734:Gatifloxacin; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D016209:Interleukin-8; D016328:NF-kappa B; D010457:Peptidoglycan; D010703:Phorbol Esters; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases; D000077734:Gatifloxacin