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Title

Interleukin-10-induced neutrophil gelatinase-associated lipocalin production in macrophages with consequences for tumor growth

AuthorsSolà, Anna M. ; Hotter, Georgina ; Brüne, Bernhard
Issue Date2012
PublisherAmerican Society for Microbiology
CitationMolecular and Cellular Biology 32(19): 3938-3948 (2012)
AbstractTumor cell-derived factors, such as interleukin 10 (IL-10), polarize macrophages toward a regulatory M2 phenotype, characterized by the expression of anti-inflammatory cytokines and protumorigenic mediators. Here we explored molecular mechanisms allowing IL-10 to upregulate the protumorigenic protein NGAL in primary human macrophages. Reporter assays of full-length or deletion constructs of the NGAL promoter provided evidence that NGAL production is STAT3 dependent, activated downstream of the IL-10-Janus kinase (Jak) axis, as well as being C/EBPβ dependent. The involvement of STAT3 and C/EBPβ was shown by chromatin immunoprecipitation (ChIP) and ChIP-Western analysis, as well as decoy oligonucleotides scavenging both STAT3 and C/EBPβ in human macrophages. Furthermore, the production of NGAL in macrophages in response to IL-10 induces cellular growth and proliferation of MCF-7 breast cancer cells. We conclude that both STAT3 and C/EBPβ are needed to elicit IL-10-mediated NGAL expression in primary human macrophages. Macrophage-secreted NGAL shapes the protumorigenic macrophage phenotype to promote growth of MCF-7 breast cancer cells. Our data point to a macrophage-dependent IL-10-STAT3-NGAL axis that might contribute to tumor progression. © 2012, American Society for Microbiology.
URIhttp://hdl.handle.net/10261/80752
DOI10.1128/MCB.00413-12
Identifiersdoi: 10.1128/MCB.00413-12
issn: 0270-7306
e-issn: 1098-5549
Appears in Collections:(IIBB) Artículos
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