scholarly journals The 6-Fluoro-8-Methoxy Quinolone Gatifloxacin Down-Regulates Interleukin-8 Production in Prostate Cell Line PC-3

2006 ◽  
Vol 51 (1) ◽  
pp. 162-168 ◽  
Author(s):  
Koh Takeyama ◽  
Hiroaki Mitsuzawa ◽  
Chiaki Nishitani ◽  
Takeyuki Shimizu ◽  
Hitomi Sano ◽  
...  

ABSTRACT 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-α), indicating that GFLX exhibits an anti-inflammatory effect on the prostate cell line. However, GFLX failed to alter activation of the NF-κB and AP-1 elicited by these stimulants. GFLX significantly attenuated the expression of IL-8 mRNA in TNF-α-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.

In Vitro ◽  
1977 ◽  
Vol 13 (2) ◽  
pp. 108-114 ◽  
Author(s):  
James S. Norris ◽  
Charles Bowden ◽  
P. O. Kohler

2009 ◽  
Vol 20 (3) ◽  
pp. 569-575 ◽  
Author(s):  
Humberto M. Spindola ◽  
João E. de Carvalho ◽  
Ana Lúcia T. G. Ruiz ◽  
Rodney A. F. Rodrigues ◽  
Carina Denny ◽  
...  

1981 ◽  
Vol 31 (6) ◽  
pp. 481-489
Author(s):  
YOSHIKAZU ITO ◽  
KOICHI KITAURA ◽  
EIKO INOUE ◽  
YOICHI NAKAZATO

1998 ◽  
Vol 330 (1) ◽  
pp. 429-435 ◽  
Author(s):  
Thierry ROGER ◽  
A. Theo OUT ◽  
Naofumi MUKAIDA ◽  
Kouji MATSUSHIMA ◽  
M. Henk JANSEN ◽  
...  

Inhibition of protein synthesis may result in superinduction of short-lived transcripts and has been attributed variably to stabilization of transcripts and/or increased gene transcription. Little is known about the kinetics of these processes and relevant transcriptional elements have not been identified. In this study, we describe superinduction of interleukin 8 (IL-8) mRNA, an important inflammatory mediator, in lung epithelial-like H292 cells and identify the underlying molecular mechanisms and their kinetics. Cycloheximide (CHI, 10 μg/ml), an inhibitor of protein synthesis, maximally increased IL-8 mRNA levels 30-fold in H292 cells. Tumour necrosis factor α (TNF-α), which induced IL-8 mRNA 3-fold, synergized with CHI causing a 150-fold increase at 6 h. CHI early on increased the stability of IL-8 mRNA (from 40 min in cells cultured with medium to more than 4 h with CHI). CHI also increased transcription as shown by transfection with IL-8 promoter constructs. Truncated and mutated constructs identified NF-κB and AP-1 binding sites as primary cis-acting elements in IL-8 gene transcription and IL-8 mRNA superinduction. Electrophoretic mobility shift assays indicated that CHI increased NF-κB and prolonged AP-1 DNA-binding activities and that the synergism of TNF-α and CHI on IL-8 mRNA expression was paralleled by a further increase of AP-1 DNA-binding activity. This synergism was still noticed when 4 h elapsed between the addition of CHI and that of TNF-α. Taken together, our results indicate that CHI interferes with both post-transcriptional and transcriptional repressive mechanisms of IL-8 mRNA expression.


2018 ◽  
Vol 55 ◽  
pp. 91-106
Author(s):  
Jéssica Costa ◽  
Rute Pereira ◽  
Jorge Oliveira ◽  
Ângela Alves ◽  
Ângela Marques-Magalhães ◽  
...  

1999 ◽  
Vol 276 (3) ◽  
pp. L426-L434 ◽  
Author(s):  
Jianping Ye ◽  
Xianglin Shi ◽  
William Jones ◽  
Yon Rojanasakul ◽  
Ningli Cheng ◽  
...  

Recent studies have demonstrated that dielectrophoresis is an efficient method for the separation of fibers according to fiber length. This method allows the investigation of fiber-cell interactions with fiber samples of the same composition but of different lengths. In the present study, we analyzed the effects of length on the interaction between glass fibers and macrophages by focusing on production of the inflammatory cytokine tumor necrosis factor (TNF)-α in a mouse macrophage cell line (RAW 264.7). The underlying molecular mechanisms controlling TNF-α production were investigated at the gene transcription level. The results show that glass fibers induced TNF-α production in macrophages and that this induction was associated with activation of the gene promoter. Activation of the transcription factor nuclear factor (NF)-κB was responsible for this induced promoter activity. The inhibition of both TNF-α production and NF-κB activation by N-acetyl-l-cysteine, an antioxidant, indicates that generation of oxidants may contribute to the induction of this cytokine and activation of this transcription factor by glass fibers. Long fibers (17 μm) were significantly more potent than short fibers (7 μm) in inducing NF-κB activation, the gene promoter activity, and the production of TNF-α. This fiber length-dependent difference in the stimulatory potency correlated with the fact that macrophages were able to completely engulf short glass fibers, whereas phagocytosis of long glass fibers was incomplete. These results suggest that fiber length plays a critical role in the potential pathogenicity of glass fibers.


2014 ◽  
Vol 29 (3) ◽  
pp. 288-290 ◽  
Author(s):  
Michele Salemi ◽  
Filippo Fraggetta ◽  
Antonio Galia ◽  
Pietro Pepe ◽  
Laura Cimino ◽  
...  

Prostate cancer (PCa) is the most frequent cancer among men in many developing countries, and the second leading cause of cancer-related death in men. A genetic component has been implicated in PCa onset and development. The cerebellar degeneration-related autoantigen 1 ( CDR1) gene, mapping in Xq26-q27.2, is expressed in cerebrum, cerebellum, heart, lung, liver, and kidney. In addition, CDR1 expression has been detected in neuroblastoma, renal carcinoma cell lines, and other cancer cell lines. In this study, we investigated the expression of the CDR1 gene in the LNCaP and PC-3 PCa cell lines, and in the PNT1A normal prostate cell line. CDR1 mRNA expression was evaluated by qRT-PCR. We found that the CDR1 gene was overexpressed in the LNCaP and PC-3 PCa cell lines as compared with the PNT1A normal prostate cell line. These data suggest that CDR1 could be a new biomarker for PCa identification.


2004 ◽  
Vol 287 (1) ◽  
pp. L52-L59 ◽  
Author(s):  
Wei Ding ◽  
Saverio Bellusci ◽  
Wei Shi ◽  
David Warburton

The expression of Sprouty4 ( Spry4), an intracellular FGF receptor antagonist, shows a temporally and spatially restricted pattern in embryonic lung and is induced by ERK signaling. To clarify the molecular mechanisms regulating Spry4 transcription, the genomic structure of the human Sprouty4 ( hSpry4) gene was first determined by using the GenomeWalker kit. The hSpry4 gene spans > 14 kb and is organized in three exons and two introns. Multiple transcription start sites were subsequently mapped by 5′-rapid amplification of cDNA ends. Analysis of up to 4 kb of sequence in the 5′-flanking region of the gene showed the presence of multiple potential transcription factor binding sites but no TATA or CAAT boxes. Transient transfection using luciferase reporter gene constructs with progressive deletions of the hSpry4 5′-flanking region revealed that the core promoter activity is located within the proximal 0.4-kb region, whereas the minimal ERK-inducible promoter activity is between −69 and −31. Homology analysis further showed that the core promoter region of the hSpry4 gene exhibits significant similarity to the 5′-flanking region of the mouse gene.


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