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Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity.

Abstract：

:The identification of soluble factors involved in stem cell renewal is a major goal in the assessment of the BM niche. We have previously shown that human endothelial cell (EC) supernatants can induce the proliferation of hematopoietic progenitor cells (HPCs), especially after stimulation with IL-1β. To identify new potential growth factors, we compared the expression profile of IL-1β-stimulated ECs over 4, 8 and 16 h with non-stimulated ECs using oligonucleotide microarrays covering more than 46,000 transcripts. Most significant changes were detected after 4 h. Utilization of Gene Ontology annotation for the stimulated EC transcriptome indicated multiple upregulated genes encoding extracellular proteins with a cell-cell signaling function. Using flow cytometry, delta, colony and cobblestone assays, we assessed the proliferative capacities of 11 gene products, i.e. IL-8, IL-32, FGF-18, osteoprotegerin, Gro 1-3, ENA78, GCP-2, CCL2 and CCL20, which are not known to induce HPC expansion. Notably, IL-32 and to a lesser degree osteoprotegerin and Gro 3 significantly induced the proliferation of HPCs. Furthermore, IL-32 attenuated chemotherapy-related BM cytotoxicities by increasing the number of HPCs in mice. Our findings confirm that the combination of microarrays and gene annotation helps to identify new hematopoietic growth factors.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Moldenhauer A,Futschik M,Lu H,Helmig M,Götze P,Bal G,Zenke M,Han W,Salama A

doi

10.1002/eji.201040986

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

1774-86

issue

6

eissn

0014-2980

issn

1521-4141

journal_volume

41

pub_type

杂志文章

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