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)

The cytokines IL-6, initially recognized as a regulator of immune and inflammatory response and IL-8, a potential regulator of angiogenesis, also regulate the growth of many tumor cells. Human cancer cells selected for multidrug resistance to common chemotherapeutic agents demonstrate increased expression of IL-6 and IL-8. To determine whether IL-6 or IL-8 overexpression contributes directly to the drug resistant phenotype, IL-6 or IL-8 cDNA were introduced into the paclitaxel sensitive human osteosarcoma cell line U-2OS using the pIRESneo bicistronic expression vector. Interleukin-6 and IL-8 transfectants were selected for either high IL-6 or IL-8 secretion and evaluated in drug resistance assays. Two IL-6 and two IL-8 secreting clones express IL-6 or IL-8 levels of 10 ng/ml and 1 ng/ml in culture, while parental U-2OS and pIRESneo vector transfected control cells express IL-6 and IL-8 levels of 0.005 ng/ml and 0.1 ng/ml, respectively. MTT cytotoxicity with IL-6 transfected cells demonstrates a five-fold increase in resistance to paclitaxel and a four-fold increase in resistance to doxorubicin as compared to U-2OS. There are no changes in mitoxantrone or topotecan resistance in the IL-6 transfectants as compared to parental U-2OS. Northern analysis of IL-6 transfectants demonstrates that the resistant phenotype is not related to increased levels of MDR-1, MRP-1, or LRP. Western analysis also confirms that P-glycoprotein levels are not altered in IL-6 transfectants. Further supporting an MDR-1 independent mechanism of drug resistance, verapamil cannot reverse paclitaxel resistance in transfected cells, findings further supported by rhodamine 123 exclusion data. Treatment of IL-6 transfected cells with paclitaxel, compared with drug-sensitive parental U-2OS, shows U-2OS(IL-6) are significantly more resistant to apoptosis induced by paclitaxel and exhibit decreased proteolytic activation of caspase-3. In contrast U-2OS(IL-8) transfectants demonstrate no appreciable increase in paclitaxel resistance when compared with parental cells. In summary, while both IL-6 and IL-8 are overexpressed in paclitaxel resistant cell lines, only IL-6 has the potential to contribute directly to paclitaxel and doxorubicin resistance in U-2OS. This resistance is through a non-MDR-1 pathway.
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PMID:Overexpression of IL-6 but not IL-8 increases paclitaxel resistance of U-2OS human osteosarcoma cells. 1202 4

There is growing evidence that chemokines play important roles in the immune surveillance of central nervous system (CNS). In the CNS, microglia are primary immune effector cells and secrete various chemokines in response to their microenvironment. Using the RT-PCR procedure and indirect immunofluorescence analysis, we found that CCL6 (known as C10/MRP-1 in mouse) was expressed in rat primary microglia without any stimulation, but not in primary astrocytes, although both cell types expressed CCR1 mRNA, which is a receptor for CCL6. Furthermore, immunohistochemical analysis demonstrated that microglia produced CCL6 protein in a normal brain, suggesting that microglia may be the primary source of CCL6 in a normal brain. Recombinant rat CCL6 mediated the migration of microglia and astrocytes in vitro. The CCL6-mediated cell migration was blocked by treating the cells with LY294002, a PI3-kinase inhibitor and Western blot analysis showed that the phosphorylation of Akt could be induced by treating microglia with a recombinant CCL6, suggesting that CCL6 functions by activating the PI3-kinase/Akt pathway. A proinflammatory cytokine, interferon-gamma enhanced the expression of both CCL6 mRNA and protein in microglia, while other proinflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha and an anti-inflammatory cytokine, transforming growth factor-beta exerted no effect on CCL6 expression in microglia. These findings suggest that CCL6 may be a mediator released by microglia for cell-cell communication under physiological as well as pathological conditions of CNS.
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PMID:Functional expression of CCL6 by rat microglia: a possible role of CCL6 in cell-cell communication. 1608 46