- Paper Report
- Open Access
Anti-inflammatory effects of NF-?B
- Cheryl Smythe1
© Biomed Central Ltd 2002
- Received: 17 January 2002
- Published: 17 January 2002
Inflammation is a self-resolving process during which both pro- and anti-inflammatory mediators are temporally expressed. The transcription factor NF-?B is known to positively regulate the expression of proinflammatory mediators such as cytokines, growth factors and adhesion molecules and is therefore considered to be an interesting target for therapeutic intervention. However, some evidence suggests a role for NF-?B in the resolution of the inflammatory response. Therefore using two animal models, this study investigates the role of leukocyte NF-?B throughout the inflammatory response.
NF-?B activation in leukocytes from rat carrageenin pleurisy was found to be biphasic. cRel-p50 NF-?B complexes were predominant at 6h, with increased inducible nitric oxide synthase expression. In contrast, at 48h NF-?B complexes comprised of p50-p50 homodimers were associated with increased cyclooxygenase-2 expression. The NF-?B inhibitor PDTC significantly reduced the exudate volume and the number of extravasated leukocytes when administered simultaneously with the carrageenin challenge (prophylactically). However, if administered 24h after challenge (therapeutically), exudate volume and leukocyte number increased, while the level of TGF-? and the number of apoptotic leukocytes decreased. Temporal gene expression analysis demonstrated that levels of lymphotoxin ?, TNF-a and the anti-apoptotic protein Bcl2 were elevated 6h after challenge, while TGF-&946;1 and the proapoptotic Bcl2 homolog Bax were expressed at 48h. Expression of lymphotoxin ? and TNF-a was inhibited at 6h if the NF-?B inhibitor was administered prophylactically. However if administered therapeutically, expression of TGF-?1 and Bax was reduced, and processing of p105 to p50 was inhibited.
Carrageenin-induced pleurisy, mouse carrageenin air pouch, electrophoretic mobility-shift assay, ELISA, western blotting, annexin V apoptosis and RNase protection assays