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- Title
Mitochondrial Ca²+ and ROS take center stage to orchestrate TNF-α-mediated inflammatory responses.
- Authors
Dada, Laura A; Sznajder, Jacob I
- Abstract
Proinflammatory stimuli induce inflammation that may progress to sepsis or chronic inflammatory disease. The cytokine TNF-α is an important endotoxin-induced inflammatory glycoprotein produced predominantly by macrophages and lymphocytes. TNF-α plays a major role in initiating signaling pathways and pathophysiological responses after engaging TNF receptors. In this issue of JCI, Rowlands et al. demonstrate that in lung microvessels, soluble TNF-α (sTNF-α) promotes the shedding of the TNF-α receptor 1 ectodomain via increased mitochondrial Ca²+ that leads to release of mitochondrial ROS. Shedding mediated by TNF-α-converting enzyme (TACE) results in an unattached TNF receptor, which participates in the scavenging of sTNF-α, thus limiting the propagation of the inflammatory response. These findings suggest that mitochondrial Ca²+, ROS, and TACE might be therapeutically targeted for treating pulmonary endothelial inflammation.
- Publication
The Journal of clinical investigation, 2011, Vol 121, Issue 5, p1683
- ISSN
1558-8238
- Publication type
Journal Article
- DOI
10.1172/JCI57748