Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antimicrobial agents have been reported to exhibit immunomodulatory and anti-inflammatory activities, both in vivo and in vitro (e.g., in human lymphocytes, macrophages and monocytes). The effects of moxifloxacin on cytokine immunomodulatory mediators, free radical generation and hydrolytic enzyme activities in zymogen A-stimulated human THP-1 monocytes were evaluated. An increase in c-AMP levels, protein kinase C activity, and the release of nitric oxide and hydrogen peroxide with a decrease in pH occurred within the first hour. Further, the effects of moxifloxacin were reduced by agents which blocked the oxygen burst, lysosome-phagosome fusion, and the energy generation within the cell. After 4 h, there was a decrease in NAG and cathepsin D activities, lipid peroxidation and the release of pro-inflammatory cytokines. These data indicate that moxifloxacin may modify the acute-phase inflammatory responses through inhibition of cytokine release in monocytes. Moxifloxacin inhibited the release of TNFalpha, IL-1, IL-6, and IL-8 in a concentration-dependent manner across a range of 0.004 to 4 microg/mL. After 4 h, there was a decrease in the release of these cytokines, thus interfering with the inflammation process to reduce infection and its spread. The effects of moxifloxacin appear initially to activate monocytes to kill bacteria through the innate immune process by releasing ROS and lysosomal hydrolytic enzymes as well as phagocytosis of the organism. At a later time the bacteria are killed through a Bacterialstatic mechanism of protein synthesis inhibition and there is a reversal of the effects of moxifloxacin on cytokine release, free radical generation and hydrolytic enzymes so that lipid peroxidation and tissue destruction by the infection process is suppressed.
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PMID:Effects of moxifloxacin in zymogen A or S. aureus stimulated human THP-1 monocytes on the inflammatory process and the spread of infection. 1367 36

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) (P<0.004). 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) (P<0.04). 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 microg ml(-1) VP-16, and decreased IL-8 release from cells incubated for 72 h with 3 microg ml(-1) VP-16 (P<0.001). VP-16 enhanced the release of IL-1beta and TNF-alpha from THP-1 cells, whereas the addition of MXF prevented the enhanced cytokine secretion (P<0.001). 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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PMID:Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells. 1704 52

Epithelia in the human airways, from the nasal aperture to the alveoli, are covered in a protective film of fluid containing a number of antimicrobial proteins. Defensins are single-chain, strongly cationic peptides and are one of the most extensively studied classes of antimicrobial peptides. Moxifloxacin (MXF) is a fluoroquinolone that acts against both Gram positive and Gram negative bacteria. In this study, we evaluated the effects of HBD2, MXF and the association MXF/HBD2 on some cytokines and on the ICAM-1 expression in LPS-stimulated A549 cells. Our results suggest that by lowering the epithelial cell-derived IL-1beta, IL-6, IL-8 and ICAM-1 expression, the MXF/HBD2 association interferes with the multifunctional cytokine network evolving during inflammatory processes of the respiratory tract; this anti-inflammatory potential could be of great value in the treatment of inflammatory disorders.
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PMID:Anti-inflammatory effects of moxifloxacin and human beta-defensin 2 association in human lung epithelial cell line (A549) stimulated with lipopolysaccharide. 1799 31

Camptothecins (CPTs) are topoisomerase I (topo I) inhibitor chemotherapeutic agents. Studies indicate that combination therapy is needed in most therapeutic protocols with camptothecins. Certain fluoroquionolones inhibit topoisomerase II activity in eukaryotic cells. We showed previously that the fluoroquionolone moxifloxacin inhibited purified human topoisomerase II, acted synergistically with etoposide and enhanced anti-proliferative effect in THP-1 and Jurkat cells. There is no information on flouroquionolone's activity on topoisomerase I. We examined the effect of moxifloxacin and ciprofloxacin alone or in combination with camptothecin on purified topoisomerase I activity and further analysed their combined activity on proliferation and apoptosis in HT-29 cells. Moxifloxacin and ciprofloxacin alone slightly inhibited purified topoisomerase I activity; however in combination with camptothecin it led to a 82% and 64% reduction in enzyme activity, respectively. Moreovwer, our studies indicate that incubation of HT-29 cells with a combination of moxifloxacin or ciprofloxacin with CPT increases cellular topoisomerase I inhibitory activity. In cell proliferation assays, addition of moxifloxacin to 1nM camptothecin enhanced its cytotoxic activity by three-fold and was similar to that of 50nM camptothecin alone (45+/-2.1% inhibition). Ciprofloxacin enhanced cytotoxic activity to a lesser extent. Apoptosis studies showed up to 1.6-fold increase in annexin V positive cells when the fluoroquinolones were combined with camptothecin as compared to camptothecin alone. Analysis of the proangiogenic factors IL-8 and VEGF showed significant reduction in IL-8 production by moxifloxacin and ciprofloxacin up to 48% and in VEGF secretion from the cells. Further in vivo and clinical studies of camptothecins combined with the above fluoroquinolones are warranted.
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PMID:Quinolones as enhancers of camptothecin-induced cytotoxic and anti-topoisomerase I effects. 1819 Nov 6