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Possible new role for NF-κB in the resolution of inflammation

Abstract

Inflammation involves the sequential activation of signaling pathways leading to the production of both pro- and anti-inflammatory mediators. Although much attention has focused on pro-inflammatory pathways that initiate inflammation, relatively little is known about the mechanisms that switch off inflammation and resolve the inflammatory response. The transcription factor NF-κB is thought to have a central role in the induction of pro-inflammatory gene expression and has attracted interest as a new target for the treatment of inflammatory disease. We show here that NF-κB activation in leukocytes recruited during the onset of inflammation is associated with pro-inflammatory gene expression, whereas such activation during the resolution of inflammation is associated with the expression of anti-inflammatory genes and the induction of apoptosis. Inhibition of NF-κB during the resolution of inflammation protracts the inflammatory response and prevents apoptosis. This suggests that NF-κB has an anti-inflammatory role in vivo involving the regulation of inflammatory resolution.

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Figure 1: NF-κB activation in leukocytes during inflammation.
Figure 2: Effects of PDTC on inflammatory parameters.
Figure 3: Inhibition of NF-kB or COX2 activity protracts the inflammatory response in vivo.
Figure 4: Effects of the NF-κB inhibitors PDTC and MG132 on leukocyte apoptosis and TGF-β1 release during the resolution of rat carrageenin pleurisy.
Figure 5: Analysis of cytokine and apoptosis related gene expression in carrageenin pleurisy.
Figure 6: Effects of MG132 treatment during inflammation.

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Correspondence to Toby Lawrence.

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Lawrence, T., Gilroy, D., Colville-Nash, P. et al. Possible new role for NF-κB in the resolution of inflammation. Nat Med 7, 1291–1297 (2001). https://doi.org/10.1038/nm1201-1291

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