Published online Dec 9, 2015. doi: 10.5497/wjp.v4.i4.265
Peer-review started: June 1, 2015
First decision: August 4, 2015
Revised: September 10, 2015
Accepted: October 16, 2015
Article in press: October 19, 2015
Published online: December 9, 2015
Core tip: Extracellular signal-regulated kinases 1/2 and p38 mitogen activated protein kinase cascades are activated in response to stimulation with inflammatory stimuli, including lysophosphatidic acid, and are able to activate mitogen- and stress-activated kinase (MSK) 1 and MSK2 in human synovial fibroblasts. MSKs then phosphorylate the transcription factor cAMP response element-binding protein (CREB), leading to the production of pro-inflammatory and anti-inflammatory cytokines. In addition to CREB, many other downstream effectors of MSK1/2 such as nuclear factor-kappa B, histone H3, the E3 ubiquitin ligase, Tripartite motif containing 7 and high mobility group nucleosome binding domain 1 have been reported and suggested to play important functions in immunity and disease states, including arthritis.