Mitochondrial Ca2+ and ROS take center stage to orchestrate TNF-α-mediated inflammatory responses

Research output: Contribution to journalComment/debatepeer-review

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1683-1685
Number of pages3
JournalJournal of Clinical Investigation
Volume121
Issue number5
DOIs
StatePublished - May 2 2011

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Mitochondrial Ca<sup>2+</sup> and ROS take center stage to orchestrate TNF-α-mediated inflammatory responses'. Together they form a unique fingerprint.

Cite this