interleukin-8 and peoniflorin

Liver diseases are closely associated with elevated levels of interleukin-8 (IL-8), suggesting the ability to inhibit IL-8 production could enhance the treatment of liver diseases. Paeoniflorin is a major active constituent of dried Paeoniae Radix Alba root (Baishao in Chinese) which is widely used in China to treat liver diseases. We examined the effects and underlying mechanisms of paeoniflorin on IL-8 production in primary human hepatic sinusoidal endothelial cells (HHSECs). Concanavalin A (ConA) at 20 μg/mL produced a 5.2-fold increase in IL-8 mRNA by 8h, and a 14.2-fold rise in IL-8 levels by 16 h. Inhibition of MEK (ERK kinase) and extracellular signal-regulated kinase (ERK) by PD98059 and U0126, or inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 blocked both ConA-induced IL-8 mRNA expression and IL-8 secretion. Paeoniflorin reduced ConA-induced IL-8 mRNA expression and IL-8 release by 57.9% and 52.8%, respectively, and also decreased ConA-stimulated phosphorylation of ERK1/2 and Akt, suggesting paeoniflorin inhibits IL-8 expression and release by inhibiting the ERK1/2 and Akt pathways. Combining paeoniflorin with U0126 or LY294002 at low doses showed supra-additive inhibition of not only phospho-ERK1/2 and phospho-Akt by 46.4% and 35.0%, but also IL-8 release by 42.4% and 36.1% and IL-8 mRNA expression by 43.5% and 31.8%, respectively. In conclusion, paeoniflorin most likely contributes to the therapy for liver disease by exerting anti-inflammatory effects on HHSECs through blocking IL-8 secretion via downregulation of ERK1/2 and Akt phosphorylation.

Topics: Anti-Inflammatory Agents; Cells, Cultured; Concanavalin A; Down-Regulation; Endothelial Cells; Extracellular Signal-Regulated MAP Kinases; Glucosides; Humans; Interleukin-8; Liver; MAP Kinase Signaling System; Monoterpenes; Oncogene Protein v-akt; Phosphorylation; Primary Cell Culture

Ginsenoside Rb1 (GRb1) and paeoniflorin (PF) are active substances of Chinese traditional herbs and have been commonly used to treat skin inflammation diseases, but little is known about the mechanisms involved. In the present study, the effects of GRb1 and PF on the production of inflammatory mediators and the possible mechanisms of transient receptor potential vanilloid-1 (TRPV1) in these mediators induction were explored. It has been shown that GRb1 and PF inhibited the productions of IL-8 and PGE₂ induced by capsaicin (CAP) in HaCaT cells and HEK 293T-TRPV1 cells (which were transgenic and overexpressed TRPV1) but had no effect on HEK 293T mock cells (p<0.05). Besides, CAP was able to induce calcium influx and nuclear factor kappa B(NF-κB) transcriptional activity in HaCaT cells and HEK 293T-TRPV1 cells, but had no effect on HEK 293T mock cells. Furthermore, GRb1 inhibited CAP-induced calcium influx and NF-κB transcriptional activity in both HaCaT cells and HEK 293T-TRPV1 cells. However, PF decreased CAP-induced calcium influx and NF-κB transcriptional activity only in HaCaT cells. This would suggest that GRb1 inhibits CAP-induced calcium influx and NF-κB activity through TRPV1 signal, while calcium influx and NF-κB activity might not be involved in the inhibitory effect of PF on TRPV1 signal. Furthermore, the inhibitory rates of GRb1 and PF on IL-8 and PGE₂ production were higher than those caused by capsazepine, an antagonist of TRPV1, suggesting that GRb1 and PF have great potential in clinical treatment of skin diseases.

Topics: Benzoates; Bridged-Ring Compounds; Cell Line; Gene Expression Regulation; Ginsenosides; Glucosides; Humans; Interleukin-8; Keratinocytes; Monoterpenes; NF-kappa B; TRPV Cation Channels