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Biology of recently discovered cytokines: interleukin-17--a unique inflammatory cytokine with roles in bone biology and arthritis.

Gaffen SL - Arthritis Res. Ther. (2004)

Bottom Line: IL-17 and its receptor are founding members of an emerging family of cytokines and receptors with many unique characteristics.In addition, IL-17 synergizes potently with other cytokines, placing it in the center of the inflammatory network.Strikingly, IL-17 has been associated with several bone pathologies, most notably rheumatoid arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, USA. sgaffen@acsu.buffalo.edu

ABSTRACT
IL-17 and its receptor are founding members of an emerging family of cytokines and receptors with many unique characteristics. IL-17 is produced primarily by T cells, particularly those of the memory compartment. In contrast, IL-17 receptor is ubiquitously expressed, making nearly all cells potential targets of IL-17. Although it has only limited homology to other cytokines, IL-17 exhibits proinflammatory properties similar to those of tumor necrosis factor-alpha, particularly with respect to induction of other inflammatory effectors. In addition, IL-17 synergizes potently with other cytokines, placing it in the center of the inflammatory network. Strikingly, IL-17 has been associated with several bone pathologies, most notably rheumatoid arthritis.

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Opposing roles of IL-17 in bone turnover. IL-17 is produced by T cells (particularly memory T cells), and acts on a wide variety of target cells to trigger expression of inflammatory effectors. Most of these effectors have been shown to have an impact on bone metabolism. Those factors that promote osteoclastogenesis indirectly favor bone destruction. Conversely, chemotactic factors promote neutrophil recruitment and activation, which can exert both bone protective and bone destructive effects. G-CSF, granulocyte colony-stimulating factor; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; LIX, LPS-inducible CXC chemokine; MCP, monocyte chemotactic protein; PGE2, prostaglandin E2; RANKL, receptor activator of nuclear factor-κB ligand; TNF, tumor necrosis factor.
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Figure 1: Opposing roles of IL-17 in bone turnover. IL-17 is produced by T cells (particularly memory T cells), and acts on a wide variety of target cells to trigger expression of inflammatory effectors. Most of these effectors have been shown to have an impact on bone metabolism. Those factors that promote osteoclastogenesis indirectly favor bone destruction. Conversely, chemotactic factors promote neutrophil recruitment and activation, which can exert both bone protective and bone destructive effects. G-CSF, granulocyte colony-stimulating factor; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; LIX, LPS-inducible CXC chemokine; MCP, monocyte chemotactic protein; PGE2, prostaglandin E2; RANKL, receptor activator of nuclear factor-κB ligand; TNF, tumor necrosis factor.

Mentions: Functionally, IL-17 has been classified as a pro-inflammatory mediator, based on its ability to induce a wide array of inflammatory effectors in target cells (Fig. 1). Among these are cytokines (e.g. IL-6, tumor necrosis factor [TNF]-α, IL-1β, IFN-γ, and granulocyte colony-stimulating factor), chemokines (e.g. CXC chemokine ligand [CXCL]2/MIP-2/IL-8, CXCL1/Groα /KC, CC chemokine ligand [CCL]2/MCP-1, CCL5/RANTES, and CXCL5/LIX), and other effectors (e.g. cyclo-oxygenase-2, prostaglandin E2, nitric oxide, and intercellular adhesion molecule-1; for review [8]). Moreover, IL-17 cooperates either additively or synergistically with various inflammatory cytokines or agonists, thus placing this cytokine in the midst of a complex network that amplifies inflammation (see below). In this sense, IL-17 appears to function as an activator of the innate immune system, analogous to TNF-α and IL-1β, with which it shares many target genes. However, because IL-17 is produced by T cells rather than by monocytes or other innate cells, it presumably comes into play during adaptive or memory immune responses. Consequently, the function of IL-17 may be to trigger innate immune responses shortly after a second encounter with antigen, when the memory response is activated but when concentrations of antigen are still too low to trigger a full-scale innate immune response.


Biology of recently discovered cytokines: interleukin-17--a unique inflammatory cytokine with roles in bone biology and arthritis.

Gaffen SL - Arthritis Res. Ther. (2004)

Opposing roles of IL-17 in bone turnover. IL-17 is produced by T cells (particularly memory T cells), and acts on a wide variety of target cells to trigger expression of inflammatory effectors. Most of these effectors have been shown to have an impact on bone metabolism. Those factors that promote osteoclastogenesis indirectly favor bone destruction. Conversely, chemotactic factors promote neutrophil recruitment and activation, which can exert both bone protective and bone destructive effects. G-CSF, granulocyte colony-stimulating factor; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; LIX, LPS-inducible CXC chemokine; MCP, monocyte chemotactic protein; PGE2, prostaglandin E2; RANKL, receptor activator of nuclear factor-κB ligand; TNF, tumor necrosis factor.
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Related In: Results  -  Collection

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Figure 1: Opposing roles of IL-17 in bone turnover. IL-17 is produced by T cells (particularly memory T cells), and acts on a wide variety of target cells to trigger expression of inflammatory effectors. Most of these effectors have been shown to have an impact on bone metabolism. Those factors that promote osteoclastogenesis indirectly favor bone destruction. Conversely, chemotactic factors promote neutrophil recruitment and activation, which can exert both bone protective and bone destructive effects. G-CSF, granulocyte colony-stimulating factor; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; LIX, LPS-inducible CXC chemokine; MCP, monocyte chemotactic protein; PGE2, prostaglandin E2; RANKL, receptor activator of nuclear factor-κB ligand; TNF, tumor necrosis factor.
Mentions: Functionally, IL-17 has been classified as a pro-inflammatory mediator, based on its ability to induce a wide array of inflammatory effectors in target cells (Fig. 1). Among these are cytokines (e.g. IL-6, tumor necrosis factor [TNF]-α, IL-1β, IFN-γ, and granulocyte colony-stimulating factor), chemokines (e.g. CXC chemokine ligand [CXCL]2/MIP-2/IL-8, CXCL1/Groα /KC, CC chemokine ligand [CCL]2/MCP-1, CCL5/RANTES, and CXCL5/LIX), and other effectors (e.g. cyclo-oxygenase-2, prostaglandin E2, nitric oxide, and intercellular adhesion molecule-1; for review [8]). Moreover, IL-17 cooperates either additively or synergistically with various inflammatory cytokines or agonists, thus placing this cytokine in the midst of a complex network that amplifies inflammation (see below). In this sense, IL-17 appears to function as an activator of the innate immune system, analogous to TNF-α and IL-1β, with which it shares many target genes. However, because IL-17 is produced by T cells rather than by monocytes or other innate cells, it presumably comes into play during adaptive or memory immune responses. Consequently, the function of IL-17 may be to trigger innate immune responses shortly after a second encounter with antigen, when the memory response is activated but when concentrations of antigen are still too low to trigger a full-scale innate immune response.

Bottom Line: IL-17 and its receptor are founding members of an emerging family of cytokines and receptors with many unique characteristics.In addition, IL-17 synergizes potently with other cytokines, placing it in the center of the inflammatory network.Strikingly, IL-17 has been associated with several bone pathologies, most notably rheumatoid arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, USA. sgaffen@acsu.buffalo.edu

ABSTRACT
IL-17 and its receptor are founding members of an emerging family of cytokines and receptors with many unique characteristics. IL-17 is produced primarily by T cells, particularly those of the memory compartment. In contrast, IL-17 receptor is ubiquitously expressed, making nearly all cells potential targets of IL-17. Although it has only limited homology to other cytokines, IL-17 exhibits proinflammatory properties similar to those of tumor necrosis factor-alpha, particularly with respect to induction of other inflammatory effectors. In addition, IL-17 synergizes potently with other cytokines, placing it in the center of the inflammatory network. Strikingly, IL-17 has been associated with several bone pathologies, most notably rheumatoid arthritis.

Show MeSH
Related in: MedlinePlus