Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inefficient clearance of apoptotic cells by macrophages may cause an advanced stage of apoptosis, late apoptosis. Coculturing of macrophages with late apoptotic cells leads to high production of CXC-chemokine, IL-8, or MIP-2, a murine homologue of IL-8. However, the signaling mechanism underlying the production remains largely unknown. In this study, we examined the MAP kinase activation on coculturing of macrophages with late apoptotic cells. Extracellular signal-regulated kinase (ERK)1/2, but not p38 or c-Jun N-terminal kinase, was phosphorylated as early as 5 min after interaction of macrophages with late apoptotic cells. We then examined whether or not ERK activation is involved in the production of MIP-2 by employing selective inhibitors for MAP kinase kinase 1/2, PD98059, and U0126. These inhibitors suppressed the production of MIP-2 by macrophages at the protein and mRNA levels, whereas they did not suppress phagocytosis of late apoptotic cells, as judged on confocal microscopy. These results suggest that activation of ERK is involved in the production of MIP-2 on coculturing of macrophages with late apoptotic cells.
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PMID:Activation of extracellular signal-regulated kinase 1/2 is involved in production of CXC-chemokine by macrophages during phagocytosis of late apoptotic cells. 1282 Nov 52

IL-13 dysregulation plays a critical role in the pathogenesis of a variety of inflammatory and remodeling diseases. In these settings, STAT6 is believed to be the canonical signaling molecule mediating the tissue effects of IL-13. Signaling cascades involving MAPKs have been linked to inflammation and remodeling. We hypothesized that MAPKs play critical roles in effector responses induced by IL-13 in the lung. We found that Tg IL-13 expression in the lung led to potent activation of ERK1/2 but not JNK1/2 or p38. ERK1/2 activation also occurred in mice with null mutations of STAT6. Systemic administration of the MAPK/ERK kinase 1 (MEK1) inhibitor PD98059 or use of Tg mice in which a dominant-negative MEK1 construct was expressed inhibited IL-13-induced inflammation and alveolar remodeling. There were associated decreases in IL-13-induced chemokines (MIP-1alpha/CCL-3, MIP-1beta/CCL-4, MIP-2/CXCL-1, RANTES/CCL-5), MMP-2, -9, -12, and -14, and cathepsin B and increased levels of alpha1-antitrypsin. IL-13-induced tissue and molecular responses were noted that were equally and differentially dependent on ERK1/2 and STAT6 signaling. Thus, ERK1/2 is activated by IL-13 in the lung in a STAT6-independent manner where it contributes to IL-13-induced inflammation and remodeling and is required for optimal IL-13 stimulation of specific chemokines and proteases as well as the inhibition of specific antiproteases. ERK1/2 regulators may be useful in the treatment of IL-13-induced diseases and disorders.
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PMID:ERK1/2 mitogen-activated protein kinase selectively mediates IL-13-induced lung inflammation and remodeling in vivo. 1637 21