Anti-Inflammatory Effects of Moxifloxacin on Activated Human Monocytic Cells: Inhibition of NF-κB and Mitogen-Activated Protein Kinase Activation and of Synthesis of Proinflammatory Cytokines

Weiss, Taly; Shalit, Itamar; Blau, Hannah; Werber, Sara; Halperin, Drora; Levitov, Avital; Fabian, Ina

doi:10.1128/aac.48.6.1974-1982.2004

Cited by 97 publications

(68 citation statements)

References 48 publications

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“…The inhibitory effect of MXF on cytokine secretion from THP-1 cells also confirms our previous observations of MXF inhibition of the synthesis of proinflammatory cytokines in THP-1 cells and human peripheral blood monocytes stimulated with LPS-phorbol myristate acetate (Weiss et al, 2004) or Aspergillus fumigatus (Shalit et al, 2006). Additionally, MXF inhibited NF-kB and mitogen-activated protein kinase activation in THP-1 cells and in a human respiratory epithelial cell line (Weiss et al, 2004;Werber et al, 2005).…”

Section: Discussionsupporting

confidence: 88%

“…Additionally, MXF inhibited NF-kB and mitogen-activated protein kinase activation in THP-1 cells and in a human respiratory epithelial cell line (Weiss et al, 2004;Werber et al, 2005). Using a murine model of Candida pneumonia in immune-suppressed animals, we found that MXF exerted a protective anti-inflammatory effect, resulting in a marked decrease in bronchopneumonia and enhanced survival.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that the fluoroquinolone moxifloxacin (MXF) inhibits nuclear factor kappa B (NF-kB) activation, mitogen-activated protein kinase activation and synthesis of the proinflammatory cytokines IL-8, TNF-a and IL-lb in activated human monocytic cells (Weiss et al, 2004). It also had a protective anti-inflammatory effect in vivo in a model of Candida albicans pneumonia in immune suppressed animals, resulting in enhanced survival and reduction in IL-8 and TNF-a in lung homogenates (Shalit et al, 2002).…”

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confidence: 99%

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Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

et al. 2006

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Etoposide (VP-16) is a topoisomerase II (topo II) inhibitor chemotherapeutic agent. Studies indicate that VP-16 enhances proinflammatory cytokines secretion from tumour cells, including IL-8, a chemokine associated with proangiogenic effects. Fluoroquinolones inhibit topo II activity in eukaryotic cells by a mechanism different from that of VP-16. The fluoroquinolone moxifloxacin (MXF) has pronounced anti-inflammatory effects in vitro and in vivo. We studied the effects of MXF and VP-16 on purified human topo II activity and further analysed their combined activity on proliferation, apoptosis and caspase-3 activity in THP-1 and Jurkat cells. Moxifloxacin alone slightly inhibited the activity of human topo II; however, in combination with VP-16 it led to a 73% reduction in enzyme activity. VP-16 inhibited cell proliferation in a time and dose-dependent manner. The addition of moxifloxacin for 72 h to low-dose VP-16 doubled its cytotoxic effect in THP-1 and Jurkat cells (1.8-and 2.6-fold decrease in cell proliferation, respectively) (Po0.004). Moxifloxacin given alone did not induce apoptosis but enhanced VP-16-induced apoptosis in THP-1 and Jurkat cells (1.8-and two-fold increase in annexin V positive cells and caspase-3 activity, respectively) (Po0.04). VP-16 induced the release of IL-8 in a time and dose-dependent manner from THP-1 cells. Moxifloxacin completely blocked the enhanced release of IL-8 induced by 0.5 and 1 mg ml À1 VP-16, and decreased IL-8 release from cells incubated for 72 h with 3 mg ml À1 VP-16 (Po0.001). VP-16 enhanced the release of IL-1b and TNF-a from THP-1 cells, whereas the addition of MXF prevented the enhanced cytokine secretion (Po0.001). We conclude that MXF significantly enhances VP-16 cytotoxicity in tumour-derived cells while preventing VP-16-induced proinflammatory cytokine release. This unique combination may have clinical benefits and cytotoxic drug 'sparing effect' and should be further studied in vivo.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

et al. 2006

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“…These observations confirm our previous studies that demonstrated significant inhibition by MXF of the synthesis of proinflammatory cytokines in THP-1 cells and in human peripheral blood monocytes stimulated with LPS-phorbol myristate acetate (37) or Aspergillus fumigatus (38). The combined effect of MXF on inhibition of VP-16-induced IL-8 and of spontaneous secretion of VEGF from HT-29 cells may be an important aspect of MXF activity.…”

Section: Discussionsupporting

confidence: 91%

Moxifloxacin enhances etoposide-induced cytotoxic, apoptotic and anti-topoisomerase II effects in a human colon carcinoma cell line

Fabian¹

2010

Int J Oncol

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Abstract. Etoposide (VP-16) is a topoisomerase-II (topo II) inhibitor chemotherapeutic agent. Studies have shown that a combination of VP-16 with other drugs demonstrates better clinical responses. The aim of this study was to investigate the effects of moxifloxacin (MXF) and VP-16 on cellular topo II activity in drug-treated cells and evaluate the influence of MXF on the mode of action of VP-16, on proliferation and apoptosis of HT-29 cells. Decatenation assay, band depletion and Western blot analysis, cytotoxic assay (MTT), flow cytometric studies (cell cycle and survivin expression), apoptosis (DAPI-sulforhodamine staining and caspase 3 activity) and IL-8 and VEGF secretion were determined. MXF or VP-16 slightly affected cellular topo II activity in nuclear extracts derived from drug-treated cells while the combination enhanced inhibitory activity and the reduction in band depletion of topo II. VP-16 induced cell cycle arrest at G 2 /M and the appearance of the subG 1 peak which was increased by the addition of MXF. Apoptosis studies (DAPI staining and caspase 3 activity) showed a marked increase in the presence of MXF and VP-16 compared to VP-16 alone. VP-16 induced the release of IL-8, and addition of MXF reduced enhanced release and the spontaneous release of VEGF from the cells. In conclusion, the results suggest that the enhancement in the reduction of topo II activity by the combined MXF/VP-16 treatments was probably due to the increase in the level of the DNA-enzyme cleavable complexes formed by both drugs. The unique combination of MXF/VP-16 may have clinical benefits and a cytotoxic drug 'sparing effect' and should be further studied in vivo.

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“…ciprofloxacin or moxifloxacin may exert anti-inflammatory effects besides their well-established antimicrobial properties, as suggested by various in vitro studies [55][56][57][58]. However, in an experimental pneumonia model comparing moxifloxacin with the standard regimen of β-lactam therapy, no such effect could be detected [59].…”

Section: Beyond Bacterial Killing: Immunomodulating Effects Of Antibimentioning

confidence: 99%

Therapeutic strategies in pneumonia: going beyond antibiotics

et al. 2015

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Dysregulation of the innate immune system drives lung injury and its systemic sequelae due to breakdown of vascular barrier function, harmful hyperinflammation and microcirculatory failure, which contribute to the unfavourable outcome of patients with severe pneumonia. A variety of promising therapeutic targets have been identified and numerous innovative therapeutic approaches demonstrated to improve lung injury in experimental preclinical studies. However, at present specific preventive or curative strategies for the treatment of lung failure in pneumonia in addition to antibiotics are still missing. The aim of this mini-review is to give a short overview of some, but not all, adjuvant therapeutic strategies for pneumonia and its most important complications, sepsis and acute respiratory distress syndrome, and briefly discuss future perspectives. @ERSpublications A review of preclinical and clinical research on adjuvant therapies for pneumonia

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Anti-Inflammatory Effects of Moxifloxacin on Activated Human Monocytic Cells: Inhibition of NF-κB and Mitogen-Activated Protein Kinase Activation and of Synthesis of Proinflammatory Cytokines

Abstract: We previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory effects in immunosup-

Cited by 97 publications

References 48 publications

Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

Moxifloxacin enhances etoposide-induced cytotoxic, apoptotic and anti-topoisomerase II effects in a human colon carcinoma cell line

Therapeutic strategies in pneumonia: going beyond antibiotics

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