Additionally, NK4 reduced the phosphorylation level of NF-κB p65 and upregulated the expression of sirt1, but did not change the levels of p38 and p-p38 in RA-FLS and MH7A cells.
Additionally, pseurotin A ameliorated the protein expressions of osteoprotegerin, nuclear factor of activated T-cells, nuclear factor-kappa beta (NF-κB), IκBα, extracellular signal regulated kinase, and P38 as well as histopathological changes in the synovial tissue of CIA-induced RA rats.
Bioinformatics analysis indicated that the cytokine imbalance relevant to key molecules (such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), colony-stimulating factor 3 (CSF3), interleukin- (IL-) 6, and interferon gene (IFNG)) and canonical signaling pathways (such as the complement system, antigen presentation, macropinocytosis signaling, nuclear factor-kappa B (NF-<i>κ</i>B) signaling, and IL-17 signaling) was responsible for the common comprehensive mechanism of PS and RA.
Furthermore, ROS generation, p47phox-Ser345 phosphorylation, and ERK1/2 and p38 MAPK phosphorylation were increased in synovial neutrophils from rheumatoid arthritis (RA) patients, and TAT-Ser345 peptide inhibited ROS production by these primed neutrophils.
IL-18 induced phosphorylation of JNK, PKCdelta, p38 MAPK, and activating transcription factor 2 (ATF-2) in RA ST fibroblasts in a time-dependent manner, with JNK-2 being upstream of PKCdelta, ATF-2, and NFkappaB.
Inhibition of human rheumatoid arthritis synovial cell survival by hecogenin and tigogenin is associated with increased apoptosis, p38 mitogen-activated protein kinase activity and upregulation of cyclooxygenase-2.
Inhibitors of p38 MAPK or JNK activation provide protection against inflammation and fibrosis in animal models of kidney disease; however, clinical trials of p38 MAPK and JNK inhibitors in other diseases (rheumatoid arthritis and pulmonary fibrosis) have been disappointing.
The mitogen-activated protein kinase p38α pathway has been an attractive target for the treatment of inflammatory conditions such as rheumatoid arthritis.
The availability of potent and selective p38 mitogen activated protein kinase inhibitors provide a means in further dissecting the pathways implicated in cytokine production, which in turn maintain the chronicity of RA.
The S100A8A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis.
Therefore, we sought to determine if the tumor suppressor gene product retinoblastoma (Rb), a negative regulator of cell cycle activity, inhibits IL-6, MMP-1, and p38 in RA synovial fibroblasts.
Thus, our data show that developing specific inhibitors of the alpha-isoenzyme of p38 would be beneficial for the treatment of inflammation-induced bone destruction as observed in rheumatoid arthritis.