In vivo interstitial migration of primitive macrophages mediated by JNK-matrix metalloproteinase 13 signaling in response to acute injury.

摘要: Interstitial cell migration through extracellular matrix is a hallmark of the inflammation response, tumor invasion, and metastasis. We have established stable zebrafish transgenic line expressing enhanced GFP under lysozyme C promoter for visualizing measuring primitive macrophage in vivo. show that tissue-resident macrophages migrate rapidly to site acute injury induced by tail transection. Mechanistically, specific inhibition JNK, but not p38 ERK, dramatically abolished chemotactic dose-dependent manner, suppressing trauma-induced recruitment phosphorylated C-Jun transcription factor proximal AP-1 sites metalloproteinase 13 (mmp13), gene specifically expressed during embryogenesis required interstitial migration. Furthermore, dexamethasone suppressed JNK phosphorylation accompanied simultaneous up-regulation mkp-1, well-known phosphatase capable inactivating JNK. The results indicate JNK-Mmp13 signaling pathway plays an essential role regulating innate immune response severe