IL-14 cctivators function by triggering specific cellular pathways that result in the transcriptional upregulation of IL-14. The activation of PKC by compounds like prostratin and bryostatin 1 leads to downstream effects on transcription factors such as NF-κB and AP-1, which are known to associate with the IL-14 promoter region and stimulate its transcription.
Similarly, agents that increase intracellular cAMP levels, such as isoproterenol, forskolin, rolipram, and roflumilast, activate the CREB transcription factor, another molecule that can enhance the transcription of IL-14. This mechanism is of particular significance as it demonstrates how modulation of second messenger systems can transduce signals leading to cytokine expression alterations. Furthermore, compounds like curcumin, resveratrol, and sulforaphane exert their effects by modulating NF-κB, a central regulator of immune and inflammatory responses, which in turn can influence IL-14 levels. The activation of NF-κB can either be through direct inhibition of its inhibitors, as seen with curcumin, or through altering cellular redox states, as observed with sulforaphane. Quercetin and capsaicin further demonstrate the indirect approach to activating IL-14 by stabilizing NF-κB transcription complexes and inducing calcium influx, respectively, underscoring the complex network of signaling events that can culminate in increased IL-14 activity.
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