Interleukin‐10 is a growth factor for human melanoma cells and down‐regulates HLA class‐I, HLA class‐II and ICAM‐1 molecules

Yue, Feng Yun; Dummer, Reinhard; Geertsen, Ralf; Hofbauer, Günther F.L.; Laine, Elisabeth; Manolio, Silvana; Burg, Günter

doi:10.1002/(sici)1097-0215(19970516)71:4<630::aid-ijc20>3.3.co;2-h

Cited by 33 publications

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“…TNF-a, 44 granulocyte±macrophage colony-stimulating factor, 45,46 or transforming growth factor-b. 47 The autocrine stimulation of cell proliferation by IL-10 has been previously observed in other cell lines, such as human melanoma 18 and myeloma cells. 19 However, its role in vivo has not been demonstrated.…”

Section: Discussionmentioning

confidence: 81%

“…IL-10 increased cell proliferation in vitro and tumour growth in vivo by a direct autocrine stimulation of B16-melanoma cells It has been shown that IL-10 can be an autocrine growth factor. 18 Cell proliferation of IL-10-transfected and nontransfected cells was measured in vitro to explore the possibility that IL-10 could induce cell proliferation in an autocrine manner. Consistent with the in vivo results, the three transfected cell lines (B16-10, B16-5 and B16-13) grew faster than the control non-transfected cells (B16-0; P<0 .…”

Section: Il-10-transfected Cells Grew Faster Than Non-transfected B16mentioning

confidence: 99%

“…16 It has been shown that IL-10 can be an autocrine growth factor in culture cells. 18,19 The participation of this mechanism in cell proliferation has not been previously studied in tumour models and it is not known if contradictory results related to the effect of IL-10 on tumour growth could be associated with a different behaviour of the tumour cells in this autocrine pathway. To construct a global view of the role of IL-10 in tumour growth, it is important to dissect its direct function as an autocrine proliferation factor from its contribution to induce immune surveillance escape.…”

Section: Introductionmentioning

confidence: 99%

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Interleukin‐10 promotes B16‐melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation

et al. 2002

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Summary The aim of this study was to investigate the mechanisms by which interleukin‐10 (IL‐10) induces tumour growth in a mouse‐melanoma model. A B16‐melanoma cell line (B16‐0) was transfected with IL‐10 cDNA and three clones that secreted high (B16‐10), medium and low amounts of IL‐10 were selected. Cell proliferation and IL‐10 production were compared in vitro, and tumour growth, percentages of necrotic areas, tumour cells positive for proliferating cell nuclear antigen (PCNA), IL‐10 receptor (IL‐10R) and major histocompatibility complex type I (MHC‐I) and II (MHC‐II), as well as infiltration of macrophages, CD4+ and CD8+ lymphocytes and blood vessels were compared in vivo among IL‐10‐transfected and non‐transfected tumours. Proliferation and tumour growth were greater for IL‐10‐transfected than for non‐transfected cells (P < 0·001), and correlated with IL‐10 concentration (r ≥ 0·79, P < 0·006). Percentages of tumour cells positive for PCNA and IL‐10R were 4·4‐ and 16·7‐fold higher, respectively, in B16‐10 than in B16‐0 tumours (P < 0·001). Macrophage distribution changed from a diffuse pattern in non‐transfected (6·4 ± 1·7%) to a peripheral pattern in IL‐10‐transfected (3·8 ± 1·7%) tumours. The percentage of CD4+ lymphocytes was 7·6 times higher in B16‐10 than in B16‐0 tumours (P = 0·002). The expression of MHC‐I molecules was present in all B16‐0 tumour cells and completely negative in B16–10 tumour cells. In B16‐0 tumours, 89 ± 4% of the whole tumour area was necrotic, whereas tumours produced by B16‐10 cells showed only 4·3 ± 6% of necrotic areas. IL‐10‐transfected tumours had 17‐fold more blood vessels than non‐transfected tumours (61·8 ± 8% versus 3·5 ± 1·7% blood vessels/tumour; P < 0·001). All the effects induced by IL‐10 were prevented in mice treated with a neutralizing anti‐IL‐10 monoclonal antibody. These data indicate that IL‐10 could induce tumour growth in this B16‐melanoma model by stimulation of tumour‐cell proliferation, angiogenesis and immunosuppression.

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Section: Discussionmentioning

confidence: 81%

Section: Il-10-transfected Cells Grew Faster Than Non-transfected B16mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Interleukin‐10 promotes B16‐melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation

et al. 2002

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“…IL-10 may down-regulate MHC class I and class II expression, impeding both CTL and antibody responses, but may enhance natural killer cell activity. [6][7][8][9][10][11][12] Strong anti-HCV-specific T-helper response may contribute to self-limiting HCV infection and sustained response to interferon therapy, 30,[34][35][36][37][38] and similar effects can be attributed to HCV-specific CTL response. 30,[39][40][41][42][43][44][45] As an IL-10 antagonist, TNF presumably plays the opposing role in the inflammatory and immune responses.…”

Section: Discussionmentioning

confidence: 99%

“…For example, interleukin 10 (IL-10) is a potent anti-inflammatory Th2 cytokine that down-regulates the expression of major histocompatibility complex (MHC) class I and class II molecules as well as the production of Th1 cytokines. [6][7][8][9][10][11][12] IL-10 levels differ widely between individuals, possibly because of polymorphisms in the promoter region of the IL-10 gene. 13,14 Specifically, 3 single nucleotide polymorphisms (SNPs) in the promoter (at positions Ϫ1082, Ϫ819, and Ϫ592 relative to the transcription start site) 15 form 3 SNP combinations (ATA, ACC, GCC) associated with differential IL-10 expression.…”

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confidence: 99%

Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

et al. 2001

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Host genetic factors have been reported to influence the natural history of hepatitis C virus (HCV) infection. We examined whether variation in interleukin 10 (IL-10) and tumor necrosis factor ␣ (TNF-␣) genes would predict the likelihood of sustained response to antiviral therapy. Single nucleotide polymorphisms (SNPs) and microsatellites at two loci encoding the cytokines IL-10 and TNF-␣ were determined by polymerase chain reaction (PCR)-based techniques. Their relationship to the outcome of antiviral therapy for chronic HCV infection was studied in 49 white patients who had a virologically sustained response (SR) and in 55 white nonresponders (NR) to a combination of interferon alfa-2b and ribavirin (IFN ؉ R). Several IL-10 variants were more frequent among SRs compared with NRs. Carriage of the ؊592A or the ؊819T SNP was associated with SR (odds ratio [OR] ‫؍‬ 2.2; P ‫؍‬ .016). The ؊592A/A and the exclusively linked ؊819T/T genotypes were also associated with SR (OR ‫؍‬ 16.6; P ‫؍‬ .013 for either). The haplotype consisting of the 108-bp IL-10.R microsatellite and ؊3575T, ؊2763C, ؊1082A, ؊819T, ؊592A was also associated with SR (OR ‫؍‬ 2.65; P ‫؍‬ .01). Stratification for viral genotype, baseline viral RNA concentration, and histologic status identified homozygosity for the haplotype as the principal determinant: all 5 homozygous individuals achieved SR (OR crude ‫؍‬ 13.7; P ‫؍‬ .025; stratified ORs ‫؍‬ 1.9-7.0), whereas heterozygotes differed only slightly from wild-type carriers. In contrast, TNF alleles defined by promoter sequences ؊238G/A and ؊308G/A were approximately equally distributed among SR and NR. In conclusion, homozygosity for ؊592A, ؊819T or the extended haplotype (108bp) ؊ ( During the last decade, treatment for hepatitis C virus (HCV) infection has rapidly improved. Interferon alfa-2b in combination with ribavirin (IFN ϩ R) has become the standard regimen for HCV infection. Sustained response (SR) to IFN ϩ R, defined as undetectable HCV RNA at 6 months after discontinuation of therapy, is achievable in 30% to 60% of treated patients.

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Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma

Fujieda

Lee

Sunaga

et al. 1999

Cancer

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BACKGROUND Interleukin‐10 (IL‐10) has been implicated as an important modulator of lymphoid cells, and its sequence is homologous to an open reading frame in the Epstein–Barr virus (EBV) genome. Nasopharyngeal carcinoma (NPC) is a representative tumor related to EBV infection. METHODS The authors investigated the expression of IL‐10 in 21 primary NPCs by using an immunohistochemical approach to examine its prognostic significance. RESULTS IL‐10 staining was positive in 12 of 21 primary NPCs (57%). There was no association between IL‐10 expression and gender, tumor size, the occurrence of lymph node metastases, clinical stage, or recurrence. However, there was a significant difference in overall survival between the negative expression and positive expression of IL‐10 (P = 0.0348). Although 87.5% of the IL‐10 negative group survived for 5 years, only 15.6% of IL‐10 positive patients survived for that length of time by the Kaplan–Meier method. IL‐10 expression was significant as an independent prognostic indicator of overall survival by multivariate analysis using the Cox proportional hazards model (odds ratio, 26.64; P = 0.0019). CONCLUSIONS The results imply that expression of IL‐10 is a prognostic factor in patients with NPC and may prove valuable in selecting patients with NPC who are candidates for aggressive therapy. Cancer 1999;85:1439–45. © 1999 American Cancer Society.

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Interleukin‐10 is a growth factor for human melanoma cells and down‐regulates HLA class‐I, HLA class‐II and ICAM‐1 molecules

Cited by 33 publications

References 0 publications

Interleukin‐10 promotes B16‐melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation

Interleukin‐10 promotes B16‐melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation

Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection

Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma

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