p38 MAPK signalling cascades in inflammatory disease

Trimethylamine N‐Oxide Promotes Vascular Inflammation Through Signaling of Mitogen‐Activated Protein Kinase and Nuclear Factor‐κB

“…Of note, the peak plasma TMAO levels with this protocol were similar to levels observed in mice chronically exposed to the choline‐supplemented diet (Figure 1C) and in some human clinical studies 9, 10, 17. At 30 minutes after intraperitoneal injection of TMAO, aortas were harvested and then assessed for changes in activation of p38 mitogen‐activated protein kinase, extracellular signal–related kinase 1/2, and p65 NF‐κB, all of which have been shown to play substantial roles in cellular inflammation contributing to the development of atherosclerosis 18, 20, 21, 22, 23, 24. Immediately following injection (30 minutes), TMAO‐exposed mice showed elevated phosphorylation of functional residues on p38 mitogen‐activated protein kinase (Thr‐180/Tyr‐182), extracellular signal–related kinase 1/2 (Thr‐202/Tyr‐204), and p65 NF‐κB (Ser536) (Figure 2A and 2B).…”

Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages

“…We found that aloeemodin significantly reduced ERK1/2, JNK and p38 phosphorylation with different potency. ERK1/2 and p38 MAPK proteins are known to activate the mitogen-and stress-activated kinase (MSK) protein to regulate the NF-κB pathway (Herlaar and Brown, 1999;Nick et al, 1999;Carter, 1999;Saklatvala, 2004). Thus, aloe-emodin may inhibit the LPS-induced NF-κB pathway activation by inhibiting the phosphorylation of ERK1/2 and p38 proteins.…”

“…For instance, Akt can phosphorylate IκB, leading to NF-κB release and activation (Huang and Chen, 2009). The MAPK pathways, which are extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAPK pathways in particular (Herlaar and Brown, 1999), also regulate the synthesis of inflammation mediators at the level of transcription and translation through activation of NF-κB and AP-1 transcription factors (Kaminska, 2005).…”

Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double‐blind, methotrexate‐controlled study of patients with active rheumatoid arthritis

“…The ␣-isoform is an enzyme important to the intracellular signaling pathway for the generation of TNF␣ or IL-1␤. Multiple extracellular stimuli, including stress signals (lipopolysaccharide), osmotic or heat shock, and proinflammatory cytokines (TNF␣ or IL-1␤), stimulate the p38 pathway (4). The p38␣ MAPK also regulates the expression of cyclooxygenase 2, the enzyme that regulates prostanoids (e.g., prostaglandin E 2 ) in inflammation (5).…”