IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation

Chihara, Takashi; Suzu, Shinya; Hassan, Ranya; Chutiwitoonchai, Nopporn; Hiyoshi, Masateru; Motoyoshi, Kazuo; Kimura, Fumihiko; Okada, Seiji

doi:10.1038/cdd.2010.60

Cited by 188 publications

(211 citation statements)

References 43 publications

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“…Both in vitro and when expressed in vivo under the control of the CSF-1 promoter, the biological activities of homodimeric glycoprotein interleukin-34 (IL-34) resemble those of the secreted glycoprotein isoform of CSF-1 (Wei et al 2010). Although there are significant differences in their signaling through the CSF-1R (Chihara et al 2010), it is primarily the differential expression of IL-34 and CSF-1 (Wei et al 2010;Greter et al 2012;Nandi et al 2012;Wang et al 2012) that results in their differential spatiotemporal regulation through the CSF-1R in vivo (Wei et al 2010;Nandi et al 2012). The transmembrane and proteoglycan CSF-1 isoforms act locally (Wiktor-Jedrzejczak et al 1991;Sundquist et al 1995;Van Nguyen and Pollard 2002;Dai et al 2004;Nandi et al 2006).…”

Section: Csf-1r Expressionmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

564

521

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The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.

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Section: Csf-1r Expressionmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

564

521

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“…The approval for this study was obtained from the Kumamoto University medical ethics committee. Macrophages were prepared in the following several methods (3,10). PBMCs obtained using PANCOLL reagent (PAN Biotech, Aidenbach, Germany) were suspended in RPMI 1640 medium, 1% FCS at a density of 1 3 10 6 cells/ml, and seeded in multiwell plates or dishes.…”

Section: Human Monocyte-derived Macrophagesmentioning

confidence: 99%

“…Western blotting was performed essentially as described previously (3,10). In brief, macrophages were lysed on ice with Nonidet P-40 lysis buffer (1% Nonidet P-40, 50 mM Tris, and 150 mM NaCl) containing protease inhibitors (1 mM EDTA, 1 mM PMSF, 1 mg/ml aprotinin, 1 mg/ml leupeptin, and 1 mg/ml pepstatin) and phosphatase inhibitors (1 mM Na 3 VO 4 and 1 mM NaF).…”

Section: Western Blottingmentioning

confidence: 99%

“…Macrophage numbers were monitored using MTT reagent (10). Macrophages were cultured on 24-well tissue culture plates under different conditions.…”

Section: Macrophage Survivalmentioning

confidence: 99%

“…M-CSF (also known as CSF-1) is a primary cytokine that promotes the differentiation of monocytes into mature macrophages, as well as macrophage survival (7,8). The biological activity of M-CSF is mediated by the receptor tyrosine kinase Fms, the activation of which initiates the activation of signaling pathways such as MAPKs (9,10). The essential role of the M-CSF/Fms axis in the development of most tissue macrophages has been well established using naturally occurring M-CSF-deficient op/op mice (11,12) and Fms knockout mice (13).…”

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M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

Osman

Bhuyan

Hashimoto

et al. 2014

The Journal of Immunology

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M-CSF promotes the differentiation and survival of macrophages, and preferentially induces anti-inflammatory M2, rather than proinflammatory M1 macrophages. Recently, another cytokine, IL-32, was also shown to promote macrophage differentiation. In this article, we provide the first evidence, to our knowledge, that M-CSF has both additive and inhibitory effects on the macrophage-related activities of IL-32. When added to M-CSF–derived macrophages, M-CSF and IL-32 promoted macrophage survival, which was further enhanced by their combination. However, they had different effects on HIV-1 replication; that is, it was stimulated by M-CSF and inhibited by IL-32. Interestingly, the anti–HIV-1 activity of IL-32 was counteracted by M-CSF. Such inhibitory effect of M-CSF was not observed with IL-32–induced M1-like features including high cytokine/chemokine production and strong expression of the costimulatory molecule CD80. However, IL-32–treated macrophages unexpectedly showed also M2-like features including increased phagocytic activity, and high expression of CD14 and the scavenger receptor CD163, and the expression of CD14 and CD163 was further upregulated by cotreatment with M-CSF. The findings of this study regarding the unique functional interplay between M-CSF and IL-32 increase our understanding of the mechanisms that regulate the survival and M1/M2 ratio of macrophages, as well as HIV-1 replication in macrophages.

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Interleukins

Meager

Wadhwa

2013

Encyclopedia of Life Sciences

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The interleukins are a major class of biologically active protein mediators, known as cytokines, that following release from activated cells bind to specific cell surface receptors to induce growth and differentiating functions in target cells. Extensive studies into their genes, structures, receptors, signal transduction pathways and activities in experimental cell cultures have provided considerable knowledge leading to their molecular and biological characterisation. Fundamental findings are that they are mostly pleiotropic mediators, that is, act on more than one cell type or at different stages of cellular development, and stimulate multiple activities, especially where acting in combinations of two or more interleukins. Their production as essentially pure recombinant proteins has enabled studies in experimental model systems to determine whether their activities could be of clinical benefit, or harmful. Subsequently, several interleukins and their antagonists have been evaluated for clinical efficacy and safety in clinical studies, and have yielded promising, though not fully effective, therapeutic treatments for patients with cancer and autoinflammatory diseases. In this article, the molecular characteristics of interleukins, their cognate receptors and intracellular signalling pathways, their biological activities and their potential clinical uses are briefly described. Key Concepts: Interleukins are a broad class of biologically active proteins with hormone‐like actions that regulate the development, differentiation and functions of cells of the immune and haematopoietic systems. The activities of interleukins are mediated via cell surface receptors. Binding of interleukins to receptors triggers gene induction via the activation of intracellular signal transduction pathways. Interleukins exhibit complex biological interactions, both among themselves and with other molecular mediators, in vivo . The proinflammatory and immune‐stimulatory activities of interleukins are essential for host defence against pathogens. Interleukins can be ‘two‐edged swords’, being largely beneficial to the host at low concentrations but deleterious and toxic at high concentrations. The biological properties of interleukins have suggested their potential for development as therapeutic drugs (biopharmaceuticals) against infections and chronic diseases, such as cancer, but so far only a few have proved clinically useful. Antibody and receptor antagonists of interleukins are showing promise for the treatment of autoinflammatory and autoimmune diseases, such as irritable bowel disorders and RA.

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IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation

Cited by 188 publications

References 43 publications

CSF-1 Receptor Signaling in Myeloid Cells

CSF-1 Receptor Signaling in Myeloid Cells

M-CSF Inhibits Anti–HIV-1 Activity of IL-32, but They Enhance M2-like Phenotypes of Macrophages

Interleukins

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