Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Persistent infection with Chlamydia pneumoniae (Chlamydophila pneumoniae) has been implicated in the development of atherosclerosis, asthma and other chronic diseases. However, data on treatment of C. pneumoniae infections are limited. Microbiological failure of antimicrobial therapy has been described, even after prolonged courses of treatment with azithromycin, doxycycline and erythromycin. Gemifloxacin is an enhanced-affinity fluoroquinolone with excellent activity against most common respiratory pathogens, including C. pneumoniae. The effect of prolonged treatment with gemifloxacin, compared with azithromycin, on viability of C. pneumoniae was investigated in a continuous infection model. Gemifloxacin at final con-centrations of 0.25 and 2.5 mg/L reduced the viability of C. pneumoniae by 5 log(10), which was similar to the effect of azithromycin. However, both antimicrobials failed to completely eliminate C. pneumoniae from continuously infected cells, even after 30 days of treatment. Both antibiotics decreased levels of interleukin-6 and interleukin-8 in this model, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms.
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PMID:Effect of gemifloxacin on viability of Chlamydia pneumoniae (Chlamydophila pneumoniae) in an in vitro continuous infection model. 1200 69

Persistent infection with Helicobacter pylori confers an increased risk for the development of gastric cancer. However, the exact mechanisms whereby this bacterium causes carcinogenesis have not been completely elucidated. Recent evidence indicates that aberrant activation of the signal transducers and activators of transcription 3 (STAT3) signaling pathway may play a role in gastric carcinogenesis. Therefore, we hypothesized that H. pylori infection modulates STAT3 signaling, favoring gastric cancer development. In epithelial cells infected with H. pylori, STAT3 was activated, as assessed by immunoblotting for phosphorylated STAT3, immunofluorescence of translocated STAT3, fluorescence recovery after photobleaching, and luciferase activation in transfected cells. Activation was dependent on translocation but not phosphorylation of cytotoxin-associated gene A (CagA) in host cells. Activation seemed to be receptor-mediated because preincubation of cells with the interleukin-6 (IL-6) receptor superantagonist sant7 or inhibition of gp130 by a monoclonal antibody prevented H. pylori-mediated STAT3 activation. However, activation was not related to autocrine activation by IL-6 or IL-11. CagA+ wild-type H. pylori, but not the noncarcinogenic cagA- mutant, activated STAT3 in gastric epithelial cells in vivo in the gerbil model of H. pylori-mediated gastric carcinogenesis. Collectively, these results indicate that H. pylori CagA activates the STAT3 signaling pathway in vitro and in vivo, providing a potential mechanism by which chronic H. pylori infection promotes the development of gastric cancer.
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PMID:Helicobacter pylori cytotoxin-associated gene A activates the signal transducer and activator of transcription 3 pathway in vitro and in vivo. 1914 78

Persistent infection with high-risk human papillomavirus (HPV) is the underlying cause of ~5% of all human cancers, including the majority of cervical carcinomas and many other ano-genital and oral cancers. A major challenge remains to identify key host targets of HPV and to reveal how they contribute to virus-mediated malignancy. The HPV E6 oncoprotein aberrantly activates the signal transducer and activator of transcription 3 (STAT3) transcription factor and this is achieved by a virus-driven increase in the levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in HPV positive cervical cancers cells. Crucially, STAT3 activity is essential for the proliferation and survival of cervical cancer cells, suggesting that targeting STAT3 may have therapeutic potential. Unfortunately, the development of direct STAT3 inhibitors has been problematic in the clinic due to toxicity issues identified in early stage trials. To overcome this issue, we focused on the protein Janus kinase 2 (JAK2), which phosphorylates STAT3 and is essential for STAT3 activation. Here, we demonstrate that inhibiting JAK2 reduces cell proliferation and induces apoptosis in HPV transformed cervical cancer cells. We further establish that this is due to inhibition of phosphorylation of the JAK2 substrates STAT3 and STAT5. Finally, we demonstrate that the clinically available JAK2 inhibitor Ruxolitinib synergises with cisplatin in inducing apoptosis, highlighting JAK2 as a promising therapeutic target in HPV-driven cancers.
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PMID:JAK2 Inhibition Impairs Proliferation and Sensitises Cervical Cancer Cells to Cisplatin-Induced Cell Death. 3181 6