Expression of mitogen‐activated protein kinase phosphatase 1, a negative regulator of the mitogen‐activated protein kinases, in rheumatoid arthritis: Up‐regulation by interleukin‐1β and glucocorticoids

Abstract

Mitogen-activated protein kinases (MAPKs) are key components of intracellular signal transduction pathways that relay extracellular signals to the cell nucleus to activate transcription of genes involved in inflammation, cell migration, cell-cycle control, and apoptosis (1). The MAPKs are induced by proinflammatory cytokines such as tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), and macrophage migration inhibitory factor (MIF), and by growth factors and mediators of cellular stress, and regulate the expression of multiple proinflammatory genes, matrix metalloproteinases, and adhesion molecules (1,2). MAPK activation requires a 3-tiered cascade of protein phosphorylation, resulting in dual phosphorylation at conserved tyrosine and threonine residues. Although activation of the MAPK pathway is well described, less is known about endogenous negative regulators of MAPK, the MAPK

Corticosteroid Inhibition of Growth-Related Oncogene Protein-α via Mitogen-Activated Kinase Phosphatase-1 in Airway Smooth Muscle Cells

“…Previous investigators have used MKP-1 inhibitors, such as Ro-31-8220 and triptolide, to investigate the role of MKP-1 (21,28,29); however, we found that these inhibitors were toxic to ASMC in culture and, in addition, these inhibitors were unlikely to be selective for MKP-1. For example, Ro-31-8220 is an inhibitor of protein kinase C and raf-1, although it is claimed that this compound inhibits MKP-1 expression independent of these effects in different cell types (30,31).…”

“…For example, Ro-31-8220 is an inhibitor of protein kinase C and raf-1, although it is claimed that this compound inhibits MKP-1 expression independent of these effects in different cell types (30,31). The studies using these inhibitors demonstrate that MKP-1 is a critical negative regulator of the release of inflammatory cytokines from murine macrophages or synoviocytes (21,28,29). Using MKP-1 Ϫ/Ϫ macrophages, Zhao et al (32) demonstrated that these murine cells produce more TNF-␣, IL-6, and IL-10 when challenged with LPS compared with wild-type macrophages.…”

A formyl peptide receptor agonist suppresses inflammation and bone damage in arthritis

“…Western blotting was performed as previously described (Toh et al, 2004;Yang et al, 2013b). Briefly, cell lysates were collected using cell lysis buffer supplemented with complete mini protease inhibitor cocktail.…”

Anti-inflammatory functions of glucocorticoid-induced genes

“…It is expressed in response to GCs A Clark Anti-inflammatory functions of glucocorticoid-induced genes Page 18 of 53 in a wide variety of cell types including mast cells (Kassel et al, 2001), monocytes or macrophages (Abraham et al, 2006;Aeberli et al, 2006;Bhattacharyya et al, 2007;Chen et al, 2002;Zhao et al, 2005), microglia (Zhou et al, 2007), T lymphocytes , dermal, lung and synovial fibroblasts (Phillips et al, 2006;Toh et al, 2004;Yang et al, 2006), endothelial cells (Furst et al, 2007), osteoblasts (Engelbrecht et al, 2003;Leclerc et al, 2004), keratinocytes (Onda et al, 2006;Stojadinovic et al, 2006), adipocytes (Bazuine et al, 2004), lung epithelial cells (Chivers et al, 2006;Hermoso et al, 2004), airway smooth muscle cells (Issa et al, 2007) and HeLa cells (Imasato et al, 2002;Lasa et al, 2002). Typically expression is quite rapid (within one hour), sustained (up to 24 hours), requires relatively low concentrations of GC, and is blocked by the GR antagonist RU486.…”