Expression of proinflammatory cytokines by monocytes is tightly regulated by transcription factors such as NF-κB. In this study, we show that, in LPS-stimulated human peripheral monocytes, the pentacyclic triterpenes acetyl-α-boswellic acid (AαBA) and acetyl-11-keto-β-boswellic acid (AKβBA) down-regulate the TNF-α expression. AαBA and AKβBA inhibited NF-κB signaling both in LPS-stimulated monocytes as detected by EMSA, as well as in a NF-κB-dependent luciferase gene reporter assay. By contrast, the luciferase expression driven by the IFN-stimulated response element was unaffected, implying specificity of the inhibitory effect observed. Both AαBA and AKβBA did not affect binding of recombinant p50/p65 and p50/c-Rel dimers to DNA binding sites as analyzed by surface plasmon resonance. Instead, both pentacyclic triterpenes inhibited the LPS-induced degradation of IκBα, as well as phosphorylation of p65 at Ser536 and its nuclear translocation. AαBA and AKβBA inhibited specifically the phosphorylation of recombinant IκBα and p65 by IκBα kinases (IKKs) immunoprecipitated from LPS-stimulated monocytes. In line with this, AαBA and AKβBA also bound to and inhibited the activities of active human recombinant GST-IKKα and His-IKKβ. The LPS-triggered induction of TNF-α in monocytes is dependent on IKK activity, as confirmed by IKK-specific antisense oligodeoxynucleotides. Thus, via their direct inhibitory effects on IKK, AαBA and AKβBA convey inhibition of NF-κB and subsequent down-regulation of TNF-α expression in activated human monocytes. These findings provide a molecular basis for the anti-inflammatory properties ascribed to AαBA- and AKβBA-containing drugs and suggest acetyl-boswellic acids as tools for the development of novel therapeutic interventions.

MPFLR and TTM leed to good clinical results despite its own indications. For this reason-in selected cases-TTM may still be a suitable procedure for surgical treatment of patellar instability. However, patients treated by TTM (group B) revealed an increased retropatellar cartilage damage as well as significantly more pain during activity.

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