| First Author | Chiba N | Year | 2010 |
| Journal | Biochem Biophys Res Commun | Volume | 402 |
| Issue | 1 | Pages | 1-6 |
| PubMed ID | 20732300 | Mgi Jnum | J:165978 |
| Mgi Id | MGI:4839406 | Doi | 10.1016/j.bbrc.2010.08.075 |
| Citation | Chiba N, et al. (2010) Functional roles of Cot/Tpl2 in mast cell responses to lipopolysaccharide and FcepsilonRI-clustering. Biochem Biophys Res Commun 402(1):1-6 |
| abstractText | Cot/Tpl2, a member of MAP kinase kinase kinase (MAPKKK), is indispensable for the ERK activation, as well as the production of TNF-alpha, IL-1beta, IL-23, and PGE(2) in lipopolysaccharide (LPS)-stimulated macrophages. However, the expression and the functional roles of Cot/Tpl2 in mast cells have not been elucidated. The administration of LPS impairs allergic airway inflammation in a mast cell-dependent manner, and LPS stimulates mast cells to produce not only pro-inflammatory cytokines, such as IL-6 and TNF-alpha, but also Th2-type cytokines, such as IL-5, IL-10 and IL-13. Here, we examine the role of Cot/Tpl2 by using bone marrow-derived mast cells (BMMCs) from cot/tpl2 gene-deficient mice. Phosphorylation of ERKs was significantly decreased, whereas that of JNKs and p38 kinase was normal in LPS-stimulated cot/tpl2(-/-) BMMCs compared with wild-type counterparts. LPS-induced mRNA increase was significantly impaired for IL-5, IL-10, IL-13, and TNF-alpha, but was normal for IL-6, in cot/tpl2(-/-) BMMCs. On the other hand, degranulation by FcepsilonRI-clustering from cot/tpl2(-/-) BMMCs was significantly enhanced compared with the WT control. Although the phosphorylation of ERKs and p38 kinase by FcepsilonRI-clustering was similar in WT and cot/tpl2(-/-) BMMCs, the phosphorylation of Syk was significantly enhanced in cot/tpl2(-/-) BMMCs, which seemed to be due to the increased protein concentration of Syk. These results imply the functional importance of Cot/Tpl2 in mast cells during the course of allergic diseases such as asthma. |
