Gpnmb is induced in macrophages by IFN-γ and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses

Vera M. Ripoll, Katharine M. Irvine, Timothy Ravasi, Matthew J. Sweet, David A. Hume*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

The process of inflammation requires the selective expression of a suite of genes in cells of the macrophage lineage. To identify candidate regulators of inflammation, we used cDNA microarrays to compare the transcriptome of inflammatory macrophages (thioglycolate-elicited peritoneal macrophages), bone marrow-derived macrophages, nonadherent spleen cells, and fibroblasts. We identified genes that were macrophage restricted and further elevated in inflammatory macrophages, and characterized the function of one such gene, gpnmb. Gpnmb mRNA expression was enriched in myelomonocytic cell lines and macrophage-related tissues and strongly up-regulated during macrophage diferentiation. Epitope-tagged GPNMB expressed in RAW264.7 cells exhibited a perinuclear distribution and colocalized with the Golgi marker coat protein β. Upon activation of macrophages with IFN-γ and LPS, GPNMB translocated from the Golgi apparatus to vesicular compartments scattered toward the periphery. Gpnmb overexpression in RAW264.7 cells caused a 2-fold reduction in the production of the cytokines IL-6 and IL-12p40 and the inflammatory mediator NO in response to LPS. DBA mice, which have an inactivating point mutation in the gpnmb gene, exhibited reduced numbers of myeloid cells, elevated numbers of thioglycolate-elicited peritoneal macrophages, and higher levels of proinflammatory cytokines in response to LPS. Thus, GPNMB acts as a negative regulator of macrophage inflammatory responses.

Original languageEnglish (US)
Pages (from-to)6559-6566
Number of pages8
JournalJournal of Immunology
Volume178
Issue number10
StatePublished - May 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

Fingerprint

Dive into the research topics of 'Gpnmb is induced in macrophages by IFN-γ and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses'. Together they form a unique fingerprint.

Cite this