PMID:17475886

Citation	Ripoll, VM, Irvine, KM, Ravasi, T, Sweet, MJ and Hume, DA (2007) Gpnmb is induced in macrophages by IFN-gamma and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses. J. Immunol. 178:6557-66
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 differentiation. Epitope-tagged GPNMB expressed in RAW264.7 cells exhibited a perinuclear distribution and colocalized with the Golgi marker coat protein beta. Upon activation of macrophages with IFN-gamma 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.
Links	PubMed
Keywords	Animals; Bone Marrow Cells/immunology; Bone Marrow Cells/metabolism; Bone Marrow Cells/pathology; Cell Differentiation/genetics; Cell Differentiation/immunology; Cell Line; Cell Line, Tumor; Conserved Sequence; Eye Proteins/biosynthesis; Eye Proteins/genetics; Eye Proteins/physiology; Feedback, Physiological/genetics; Feedback, Physiological/immunology; Humans; Inflammation Mediators/metabolism; Inflammation Mediators/physiology; Interferon-gamma/physiology; Lipopolysaccharides/pharmacology; Macrophage Activation/genetics; Macrophage Activation/immunology; Macrophages/immunology; Macrophages/metabolism; Macrophages/pathology; Membrane Glycoproteins/biosynthesis; Membrane Glycoproteins/genetics; Membrane Glycoproteins/physiology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Mutant Strains; RNA, Messenger/antagonists & inhibitors; RNA, Messenger/biosynthesis; RNA, Messenger/genetics; Repressor Proteins/biosynthesis; Repressor Proteins/genetics; Repressor Proteins/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:GPNMB		GO:0032715: negative regulation of interleukin-6 production	ECO:0000315:		P		Figure 9	complete CACAO 5102
MOUSE:GPNMB		GO:0032695: negative regulation of interleukin-12 production	ECO:0000315:		P		Figure 9	complete CACAO 5103
MOUSE:GPNMB		GO:0032720 : negative regulation of tumor necrosis factor production	ECO:0000315:		P		Figure 9	complete CACAO 5912
MOUSE:GPNMB	involved_in	GO:0032720: negative regulation of tumor necrosis factor production	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
RAT:LITAF		GO:0050663: cytokine secretion	ECO:0000314:		P		Figure 7B	complete CACAO 5105

References

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