| First Author | Guma M | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 51 | Pages | 22122-7 |
| PubMed ID | 21135226 | Mgi Jnum | J:167303 |
| Mgi Id | MGI:4867779 | Doi | 10.1073/pnas.1016401107 |
| Citation | Guma M, et al. (2010) JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis. Proc Natl Acad Sci U S A 107(51):22122-7 |
| abstractText | Rheumatoid arthritis (RA) is a chronic inflammatory disease marked by bone and cartilage destruction. Current biologic therapies are beneficial in only a portion of patients; hence small molecules targeting key pathogenic signaling cascades represent alternative therapeutic strategies. Here we show that c-Jun N-terminal kinase (JNK) 1, but not JNK2, is critical for joint swelling and destruction in a serum transfer model of arthritis. The proinflammatory function of JNK1 requires bone marrow-derived cells, particularly mast cells. Without JNK1, mast cells fail to degranulate efficiently and release less IL-1beta after stimulation via Fcgamma receptors (FcgammaRs). Pharmacologic JNK inhibition effectively prevents arthritis onset and abrogates joint swelling in established disease. Hence, JNK1 controls mast cell degranulation and FcgammaR-triggered IL-1beta production, in addition to regulating cytokine and matrix metalloproteinase biosynthesis, and is an attractive therapeutic target in inflammatory arthritis. |
