| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and Lipopolysaccharide and Acts as a Feedback Regulator of Proinflammatory Responses1
* Cooperative Research Centre for Chronic Inflammatory Diseases and Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Queensland, Australia; and
School of Molecular and Microbial Sciences, University of Queensland, Queensland, Australia
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 
. Upon activation of macrophages with IFN-
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Cooperative Research Centre for Chronic Inflammatory Diseases and by grants from the National Health and Medical Research Council of Australia.
2 Address correspondence and reprint requests to Dr. David A. Hume, Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia. E-mail address: d.hume{at}imb.uq.edu.au
3 Abbreviations used in this paper: CAGE, cap analysis gene expression; BFA, brefeldin A; BMM, bone marrow-derived macrophage; DC, dendritic cell; ER, endoplasmic reticulum; HMDM, human monocyte-derived macrophage; hprt, hypoxanthine-guanine phosphoribosyltransferase; f, forward; r, reverse; TEPM, thioglycolate-elicited peritoneal macrophage; -COP, coat protein .
This article has been cited by other articles:
|
|
 |
|
  D. A. Hume Macrophages as APC and the Dendritic Cell Myth J. Immunol., November 1, 2008; 181(9): 5829 - 5835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. He, W. Li, S.-Y. Chen, S. Zhang, Y.-T. Chen, Y. Hayashida, Y.-T. Zhu, and S. C. G. Tseng Suppression of Activation and Induction of Apoptosis in RAW264.7 Cells by Amniotic Membrane Extract Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4468 - 4475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Chang, L.-J. Raggatt, K. A. Alexander, J. S. Kuliwaba, N. L. Fazzalari, K. Schroder, E. R. Maylin, V. M. Ripoll, D. A. Hume, and A. R. Pettit Osteal Tissue Macrophages Are Intercalated throughout Human and Mouse Bone Lining Tissues and Regulate Osteoblast Function In Vitro and In Vivo J. Immunol., July 15, 2008; 181(2): 1232 - 1244. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
