Granulocyte apoptosis is a crucial part of the successful resolution of inflammation. In vitro results show that activation of NF-κB (nuclear factor κB) in granulocytes is a survival mechanism. NF-κB inhibitors increase the rate of constitutive apoptosis in neutrophils and eosinophils and cause these cells to respond to the pro-apoptotic effects of TNF-α (tumour necrosis factor-α). Results from both in vivo and in vitro experiments suggest that there are at least two important waves of NF-κB activation in inflammatory loci, which increase the expression of COX-2 (cyclooxygenase-2), itself an NF-κB controlled gene. The first wave causes the production of inflammatory mediators such as PGE2 (prostaglandin E2), allowing the establishment of inflammation. The second wave causes the synthesis of PGD2 and its metabolites that induce granulocyte apoptosis by inhibiting NF-κB activation. These metabolites may therefore be important physiological mediators controlling the resolution of inflammation. Although NF-κB is an important target for anti-inflammatory therapy, the timing of inhibition in vivo may be crucial, to ensure that production of PGD2 and its sequential metabolites can occur.
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Conference Article|
June 01 2004
Regulation of granulocyte apoptosis by NF-κB
C. Ward;
C. Ward
1
Respiratory Medicine Unit, MRC Centre for Inflammation Research, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, U.K.
1To whom correspondence should be addressed (email c.ward@ed.ac.uk).
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A. Walker;
A. Walker
Respiratory Medicine Unit, MRC Centre for Inflammation Research, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, U.K.
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I. Dransfield;
I. Dransfield
Respiratory Medicine Unit, MRC Centre for Inflammation Research, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, U.K.
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C. Haslett;
C. Haslett
Respiratory Medicine Unit, MRC Centre for Inflammation Research, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, U.K.
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A.G. Rossi
A.G. Rossi
Respiratory Medicine Unit, MRC Centre for Inflammation Research, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 Biochemical Society
2004
Biochem Soc Trans (2004) 32 (3): 465–467.
Citation
C. Ward, A. Walker, I. Dransfield, C. Haslett, A.G. Rossi; Regulation of granulocyte apoptosis by NF-κB. Biochem Soc Trans 1 June 2004; 32 (3): 465–467. doi: https://doi.org/10.1042/bst0320465
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