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

In order to elucidate the role of inflammatory cytokines in the central nervous system, we examined the production of two leukocyte chemoattractants, IL-8 and monocyte chemotactic and activating factor (MCAF) in brain tumor cell lines. The glioma cell lines tested exhibited high levels of IL-8 and MCAF mRNA expression upon stimulation with IL-1 or TNF-alpha, while none of the neuroblastoma cell lines expressed these cytokine mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 alpha and TNF-alpha and appeared very rapidly, reaching maximal levels at 3-6 hr, with substantial production of these cytokines in the culture supernatants. When various immunosuppressive drugs were tested, glucocorticoids but not other immunosuppressive drugs markedly inhibited the IL-1 or TNF-alpha-induced IL-8 and MCAF mRNA accumulation, suggesting that glucocorticoid is a potent regulator of these inflammatory cytokine production in the neural tissues. In addition, reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of IL-8 and MCAF mRNA expression in resected brain tumor tissues including glioblastoma, astrocytoma grade 2, ependymoma and medulloblastoma, indicating that these inflammatory cytokines are expressed in vivo.
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PMID:Induction and regulation of IL-8 and MCAF production in human brain tumor cell lines and brain tumor tissues. 811 36

Our previous study showed that high-grade astrocytomas often expressed high interleukin (IL)-1beta production. Coexpression of IL-1beta and IL-6 has been found in a number of glioma samples and glioma cell lines. To characterize the expression of IL-6 in the human glioma microenvironment, we investigated surgically excised human gliomas, human glioblastoma xenografts, and human glioblastoma cell lines using the reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). In the 29 primary gliomas, transcripts of IL-6 were less frequently detectable (55.6%) than those of IL-1beta (72.4%) or those of IL-10, IL-8, or IL-1alpha (>80% each). As for IL-6 gene expression, little or no transcription was observed in low-grade astrocytomas, oligodendroglial tumors, and 1 ependymoma. Strong IL-6 gene expression was found in only 5 of 9 glioblastomas. Immunohistochemically, IL-6 antigen was localized in the tumor cells and macrophages in 4 of 7 glioblastomas. In 3 glioblastomas transplanted into nude mice, both IL-1beta and IL-6 were detected only in 1, but othercytokines (IL-8, IL-10, and IL-1alpha) were detected in all 3 xenografts by RT-PCR. Two cell lines both showed IL-6 expression at the mRNA level, and in a cell line with a high level of IL-6 and IL-1beta transcripts, significant production of IL-6 was observed by IHC and ELISA. We concluded that IL-6 produced in tumor tissue may be involved in tumor progression in some glioblastomas, but not in low-grade astrocytomas and oligodendroglial tumors, and that IL-6 gene expression is closely correlated with IL-1beta expression in biopsy tissue, xenografts, and cultures of human gliomas.
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PMID:Analysis of interleukin-6 gene expression in primary human gliomas, glioblastoma xenografts, and glioblastoma cell lines. 1151 69

Macrophage migration inhibitory factor (MIF) plays a critical role in tumorigenesis. We aim to examine the association of MIF with tumor recurrence and survival of gliomas, and to determine whether MIF is a valuable prognostic predictor for glioma patients. The expression of MIF and interleukin 8 (IL-8) was evaluated in 36 high-grade gliomas (20 glioblastoma multiforme, 13 anaplastic astrocytoma, and 3 anaplastic oligoastrocytoma) and 32 low-grade gliomas (18 fibrillary astrocytoma, 5 pilocytic astrocytoma, 5 oligodendroglioma, 3 ependymoma and 1 pleomorphic xanthoastrocytoma) by immunostaining. Intratumoral microvessel density (IMD) of tumors in relation to immunostainings and clinicopathological factors were analyzed statistically as well as the follow-up data of patients. High expression of both MIF (58.8%) and IL-8 (52.9%) was significantly associated with high-grade gliomas and increased microvessels in tumors, but only high expression of MIF was closely related to tumor recurrence (P = 0.001). High expression of IL-8 exhibited a close correlation with high expression of MIF in tumors (P = 0.001). Histological grading, high expression of MIF and IL-8 correlated with patients' overall survival in univariate analysis. However, only histological grading and MIF expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis; the hazard ratios were 28.012 (P = 0.001) and 11.782 (P = 0.001), respectively. Elevated production of MIF in glioma tumor cells may contribute to tumor recurrence and a worse prognosis. MIF may serve as an independent predictive factor for prognosis of glioma patients.
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PMID:Elevated expression of macrophage migration inhibitory factor correlates with tumor recurrence and poor prognosis of patients with gliomas. 2172 55

Ependymoma (EPN) in childhood is a brain tumor with substantial mortality. Inflammatory response has been identified as a molecular signature of high-risk Group A EPN. To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN Group A inflammation. Enrichment of IL6 and STAT3 pathway genes were found to distinguish Group A EPN from Group B EPN and other brain tumors, implicating an IL6 activation of STAT3 mechanism. EPN tumor cell growth was shown to be dependent on STAT3 activity, as demonstrated using shRNA knockdown and pharmacologic inhibition of STAT3 that blocked proliferation and induced apoptosis. The inflammatory factors secreted by EPN tumor cells were shown to reprogram myeloid cells, and this paracrine effect was characterized by a significant increase in pSTAT3 and IL8 secretion. Myeloid polarization was shown to be dependent on tumor secretion of IL6, and these effects could be reversed using IL6-neutralizing antibody or IL6 receptor-targeted therapeutic antibody tocilizumab. Polarized myeloid cell production of IL8 drove unpolarized myeloid cells to upregulate CD163 and to produce a number of proinflammatory cytokines. Collectively, these findings indicate that constitutive IL6/STAT3 pathway activation is important in driving tumor growth and inflammatory cross-talk with myeloid cells within the Group A EPN microenvironment. Effective design of Group A-targeted therapy for children with EPN may require reversal of this potentially immunosuppressive and protumor pathway.
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PMID:Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma. 2596 56