| First Author | Lawrenz M | Year | 2012 |
| Journal | Mucosal Immunol | Volume | 5 |
| Issue | 2 | Pages | 129-39 |
| PubMed ID | 22157885 | Mgi Jnum | J:307010 |
| Mgi Id | MGI:6709199 | Doi | 10.1038/mi.2011.57 |
| Citation | Lawrenz M, et al. (2012) Genetic and pharmacological targeting of TPL-2 kinase ameliorates experimental colitis: a potential target for the treatment of Crohn's disease?. Mucosal Immunol 5(2):129-39 |
| abstractText | Inflammatory bowel disease is characterized by dysregulated immune responses against intestinal microflora leading to marked activation of nuclear factor-kappaB (NF-kappaB) with subsequent production of pro-inflammatory cytokines. Besides NF-kappaB, the tumor progression locus 2 (TPL-2)/extracellular signal-regulated kinase (ERK) pathway also regulates inflammatory cytokines such as interleukin-1beta and tumor necrosis factor-alpha, but its role during intestinal inflammation is incompletely understood. We analyzed the impact of TPL-2 in the dextran sulfate sodium-induced experimental colitis model. Despite normal activation of NF-kappaB, animals lacking TPL-2 developed only mild colitis with reduced synthesis of inflammatory cytokines. Further, pharmacological inhibition of the TPL-2 kinase was similarly effective in ameliorating colitis as TPL-2 deficiency without obvious side effects. Because increased TPL-2/ERK activation was seen in patients with Crohn's disease (CD) but not ulcerative colitis, our findings encourage further investigation of TPL-2 kinase as potential target for the treatment of CD patients. |
