Serum amyloid A‐induced IL‐6 production by rheumatoid synoviocytes

Abstract

In this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogenactivated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-jB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-jB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis.

Expression of Serum Amyloid A in Human Ovarian Epithelial Tumors: Implication for a Role in Ovarian Tumorigenesis

“…However, in line with the concept that inflammation plays a causative role in ovarian tumorigenesis (Cannistra 2004;Fleming et al 2006), SAA may enhance the inflammatory microenvironment of the ovarian tumors by inducing inflammatory cell recruitment (Badolato et al 1994;Xu et al 1995), cytokine production (Furlaneto and Campa 2000;Koga et al 2008), and activity of inflammationassociated nuclear factors and signaling pathways (Jijon et al 2005;Mullan et al 2006). SAA may induce the adhesion and migration of ovarian tumor cells as it does for human leukocytes (Badolato et al 1994;Xu et al 1995) and enhance tumor cell proliferation, survival, and angiogenesis as has been shown in relevance to rheumatoid arthritis (Lee et al 2006;Mullan et al 2006).…”

“…Several biologic activities/effects of SAA have been described in relevance to inflammation. These include the following: inducing adhesion, migration, and tissue infiltration of inflammatory cells (Badolato et al 1994;Xu et al 1995); enhancing activity of matrixdegrading enzymes, matrix metalloproteinases (MMPs) (Migita et al 1998;Lee et al 2005), and plasminogen activators (PAs) (Michaeli et al 2008); enhancing expression of inflammatory cytokines, chemokines, and growth factors (IL-1b, IL-6, TNFa, IL-8, G-CSF, COX-2) (Furlaneto and Campa 2000;Jijon et al 2005;Koga et al 2008); stimulating angiogenesis (Lee et al 2006;Mullan et al 2006); stimulating activity of inflammation-associated nuclear factor NFkB and signaling pathways mediated by mitogen-activated protein kinases ERK1/2, p38, and JNK (Jijon et al 2005;Mullan et al 2006).…”

A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production

“…SAA regulates chemotactic migration of some leukocytes, including monocytes and neutrophils (Badolato et al, 1994). SAA also stimulates production of several cytokines from different cell types, including monocytes, epithelial cells, and synovial cells (Jijon et al, 2005;Lee et al, 2006a;Koga et al, 2008). We have recently reported that SAA stimulates CCL2 production by human umbilical vein endothelial cells (HUVECs; Lee et al, 2009).…”

“…Previous studies have shown that the local concentration of SAA is increased in a pro-inflammatory environment by the actions of several cytokines, such as interleukin-1β, resulting in an elevation of about 1000-fold during acute-phase reactions compared to the normal state (Malle et al, 1993;Uhlar and Whitehead 1999;Urieli-Shoval et al, 2000). Recently, it has been shown that SAA has cytokine-like properties by modulating several cellular responses (Badolato et al, 1994;Jijon et al, 2005;Lee et al, 2006a;Koga et al, 2008). SAA regulates chemotactic migration of some leukocytes, including monocytes and neutrophils (Badolato et al, 1994).…”

Recent advances in neutralizing the IL-6 pathway in arthritis

“…Serum amyloid A (SAA) is often employed as one of several surrogate markers of inflammation in autoimmune arthritis. 74 Koga et al 75 showed that recombinant SAA stimulated IL-6 production by RA-FLS which also required activation of p38 kinase, the p46/p52 isoforms of JNK and NF-κB.…”