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Inflammatory Disease

sgp 130 // Soluble Glycoprotein 130

Glycoprotein 130 (gp130) is a transmembrane protein which forms a hexamer with two molecules of Interleukin 6 (IL-6) and two molecules of the interleukin 6 receptor (IL-6R). gp130 is also called IL6ST, IL6-β or CD130 and can be detected in serum in a soluble form. The presence of two different soluble gp130 in human serum (90 and 110kDa), might be the result of proteolytic cleavage and/or alternative splicing of the transmembrane protein (Narazaki et al., 1993). In opposition to IL-6R, gp130 expression is not limited to IL-6 responsive cells (Hibi et al., 1990).

MRP 8/14 // Myeloid Related Protein 8 and Myeloid Related Protein 14 (S100A8/S100A9, Calprotectin)

Calprotectin is a heterodimer of the two calcium-binding proteins Calgranulin A (S100A8) and Calgranulin B (S100A9), also called Myeloid Related Protein (MRP) 8/MRP14. These non-covalently associated proteins constituted about 45% of the protein content of neutrophils cytosol and are 40-fold more abundant in neutrophils versus monocytes (Edgeworth et al., 1991). MRP8/14 is also present in macrophages of rheumatoid polyarthritic synovialis but not in normal tissue macrophages (Odink et al., 1987). This heterodimer belong to the alarmin family.

ICAM 1 // Intercellular Adhesion Molecule 1

ICAM-1 is also known as CD54. This adhesion molecule, expressed at the surfaces of immune system and endothelial cells, is up-regulated by cytokine stimulation. ICAM-1 has 5 Ig-like domains, a transmembrane region and a small carboxyl-terminal cytoplasmic domain. ICAM1 bind two integrin: leukocyte function associated antigen (LFA1 and CD11a/CD18) and macrophage 1 antigen (Mac-1, CD11b/CD18) (Bella et al., 1998; Yang et al., 2004).

CXCL13 // C-X-C motif chemokine 13

CXCL13 (also known as BCA-1 or BLC) is a 10.46kDa protein of 88 residues. Its receptor, CXCR5, is expressed by TFH cells in the follicle (TFH outside the follicle do not express CXCR5). For example, CXCR5 is expressed in the TFH cells which help B cells to differentiate in long lived plasma cells (Tangye et al., 2013).

Blocking the internalization of CXCR5 in mouse, with an anti-CXCL13 antibody, results in impairment of B cell homing in secondary lymphoid organ. It also attenuates symptoms in a model of autoimmune encephalomyelitis (Klimatcheva et al., 2015).

CXCL10 // C-X-C motif chemokine 10

CXCL10 is a 10 kDa protein and is also known as Interferon γ-induced protein 10 (IP-10) or small-inducible cytokine B10. This cytokine is implicated in the cell migration of leukocytes and its expression is dependent on interferon γ (IFN γ) in numerous cell types (neutrophils, monocytes, T lymphocytes, endothelial cells, fibroblast, keratinocytes, and thyrocytes among others)(Antonelli et al., 2014).

CXCL8/IL8 // C-X-C motif chemokine 8 / Interleukin 8

CXCL8 was the first characterized chemokine and was initially named IL-8. CXCL8, expressed by activated Th17 helper cells, attracts and activates neutrophils cells (Walz et al., 1987).

BAFF // B Cell Activating Factor

B-cell Activating Factor (BAFF) is a member of the TNF family and induces B cell proliferation and differentiation. The soluble form of BAFF is a 152aa with a single disulfide bond (Moore et al., 1999).

This cytokine is also called tumor necrosis factor ligand superfamily member 13b (TNFSF13b), B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) among other names.

VEGF-A // Vascular Endothelial Growth Factor

Vascular Endothelial Growth Factor A (VEGF-A or VEGF) is a member of the Platelet-derived growth factor (PDGF) family and is implicated in embryogenic development, angiogenesis and vascular permeability (Coultas et al., 2005). Biological activities of VEGF-A are mediated through binding with VEGFR-1 and VEGFR-2, two related tyrosine kinases receptors (Ferrara et al., 2003). VEGF-A exist under several isoforms (at least 7 different spliced variants) which have different capacities to bind heparin and heparin-sulfate and are differentially expressed during development (Byrne et al., 2005).

TNF-α // Tumor Necrosis Factor alpha

Tumor Necrosis Factor α (TNFα) is a pleiotropic cytokine mainly produced by monocytes and macrophages. It was initially found to have a cytotoxic effect on tumor cells and took its name from this. This cytokine exists as a soluble and mature form and as an unprocessed membrane bound form. The soluble form can form an active homo-dimer and an homo-trimer (Barbara et al., 1996; Semenzato, 1990). TNF is shed from the membrane by the metalloprotease ADAM17 (or TACE) and released on the circulation were it can have its central role in the inflammatory response (Gooz, 2010; Old, 1985)

TIMP-1 // Tissue Inhibitor of Metalloproteinase 1

The MMPs family comprises at least 24 different MMPs with high sequence similarity in their catalytic domains. MMPs are synthetized as pro-enzymes which are inactive until removal of their pro-domain (Löffek et al., 2011; Nagase and Woessner, 1999). Tissue Inhibitor of Metalloproteinase family comprises 4 members. They are two-domain proteins with a N-Terminal domain of approximately 125 residues and a C terminal domain of about 65 residues (Brew et al., 2000).

TGF-β1 // Transforming Growth Factor beta 1

Transforming Growth Factor β1 (TGF-β1), an homodimer of two 12.5 kDa subunits, belongs to the TGF β superfamily which comprises Bone Morphogenetic Proteins, activins, inhibins, growth differentiation factors and myostatin. There are three isoforms of TGF β (TGF-β1, TGF-β2 and TGF-β3) encoded by three different genes. Even if these three isoforms interact with the same receptor (heterodimer of TGFR-1 and TGFR-2), they are implicated in slightly different biological functions (Lafyatis, 2014).

PGE2 // Prostaglandin E2

Prostaglandin E2, derived from arachinoic acid, is implicated in a wide variety of process: paracrine mediator of the Luteinizing Hormone surge as well as stimulating inflammation in osteoarthritis and rheumatoid arthritis (Duffy, 2015; Park et al., 2006). In osteoarthritis, its synthesis is promoted indirectly (through Cyclooxygenase-2 upregulation) by pro-inflammatory cytokines such as IL-1β and TNF-α (Martel-Pelletier et al., 2003).

Bioclinica Lab employs a competitive immunoassay for measurement of PGE2 in synovial fluid.

MPO // Myeloperoxidase

Myeloperoxidase (MPO) is the peroxidase responsible for the green tinge in pus and phlegm. Named first verdoperoxidase after its isolation from canine pus, MPO is implicated in the defense against ingested pathogens. MPO constitute approximately 5% of the total neutrophil content in protein (Klebanoff et al., 2013). MPO is glycoprotein belonging to the peroxidase-cyclooxygenase superfamily which also includes eosinophil peroxidase, lactoperoxidase and thyroid peroxidase. MPO have an additional sulfonium ion linkage (Carpena et al., 2009).

MMP-9 // Active and Pro-Matrix Metalloproteinase 9

The MMPs family comprises at least 24 different MMPs with high sequence similarity in their catalytic domains. MMPs are synthetized as pro-enzymes which are inactive until removal of their pro-domain (Löffek et al., 2011; Nagase and Woessner, 1999). MMP-9 is also called gelatinase B and its expression is induced by numerous factors including TGF-β, TNF-α and VEGF. MMP-9 degrades denatured collagens, matrix associated substrate, aggrecan and can also convert some cytokines into more active or inactive immune signals (Vandooren et al., 2013).

MMP-3 // Active and Pro-Matrix Metalloproteinase 3

The MMPs family comprises at least 24 different MMPs with high sequence similarity in their catalytic domains. MMPs are synthetized as pro-enzymes which are inactive until removal of their pro-domain (Löffek et al., 2011; Nagase and Woessner, 1999). Matrix metalloproteinase 3 (MMP-3, also known as stromelysin-1), secreted by chondrocytes and synovial cells, activates other proteases and has a broad substrate specificity for degrading extracellular matrix components (fibronectin, laminin, elastin, collagen IV, and proteoglycans)(Kim and Hwang, 2011; Murphy et al., 1991).



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