calcimycin and phorbol-12-myristate

Oleanolic acid (OA) is an active compound found in a variety of medicinal herbs and plants. Though OA has been widely attributed with a variety of biological activities, studies focused on its anti-allergic inflammation properties are insufficient.. Given the rapid increase in allergic diseases and the lack of fundamental treatment options, this study aimed to find a safe and effective therapy for allergic disorders.. We evaluated the inhibitory effect of OA on allergic inflammatory response and the possible mechanisms underlying the effect using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cell (HMC)-1, and a mouse model of compound 48/80-induced anaphylactic shock.. OA suppressed pro-inflammatory cytokine expressions in PMACI-induced HMC-1 cells by inhibiting activation of the Akt, p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription (STAT) 1 signaling pathways. Moreover, OA showed a protective effect against compound 48/80-induced anaphylactic shock through inhibition of histamine release and immunoglobulin E level via regulation of NF-κB and STAT1 activation.. The results showed that OA suppressed mast cell-mediated allergic response by transcriptional regulation. We suggest that OA has potential effect against allergic inflammatory disorders, including anaphylaxis, and might be a useful therapeutic agent for allergic disease.

Topics: Anaphylaxis; Animals; Anti-Allergic Agents; Calcimycin; Cell Line; Cytokines; Histamine Release; Humans; Inflammation; Inflammation Mediators; Male; Mast Cells; Mice, Inbred ICR; NF-kappa B; Oleanolic Acid; p-Methoxy-N-methylphenethylamine; p38 Mitogen-Activated Protein Kinases; Phorbol Esters; Proto-Oncogene Proteins c-akt; STAT1 Transcription Factor

We examined the role of PKCs and Ca

Topics: Calcimycin; Calcium; Cell Line, Transformed; Gonadotrophs; Gonadotropin-Releasing Hormone; Ionomycin; Isoenzymes; Models, Biological; p38 Mitogen-Activated Protein Kinases; Peptides; Phorbol Esters; Phosphorylation; Protein Kinase C; Protein Kinase Inhibitors; src-Family Kinases; Time Factors

Salidroside [2-(4-hydroxyphenyl)ethyl β-D-gluco-pyranoside (SAS)] has been identified as the most potent ingredient of the plant Rhodiola rosea L. Previous studies have demonstrated that it possesses a number of pharmacological properties, including anti-aging, anti-fatigue, antioxidant, anticancer and anti-inflammatory properties. In this study, to ascertain the molecular mechanisms responsible for the anti-inflammatory activity of SAS, we used phorbol-12-myristate-13-acetate (PMA) plus A23187 to induce inflammation in human mast cell line-1 (HMC-1). The HMC-1 cells were treated with SAS prior to being stimulated with PMA plus A23187. Pro-inflammatory cytokine production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Western blot analysis was used to examine the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). SAS inhibited the mRNA expression and production of interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF). In cells stimulated with PMA plus A23187, SAS suppressed the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-jun N-terminal kinase 1/2 (JNK1/2), but not that of p38 MAPK. SAS suppressed the expression of NF-κB in the nucleus. On the whole, our results suggest that SAS exerts an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines through the blocking of the NF-κB and MAPK signaling pathways.

Topics: Anti-Inflammatory Agents; Calcimycin; Cell Line, Tumor; Cytokines; Gene Expression Regulation; Glucosides; Humans; Inflammation; Inflammation Mediators; Mitogen-Activated Protein Kinases; NF-kappa B; Phenols; Phorbol Esters; Signal Transduction

Long-term (18 h) activation of 5-HT1A receptors alters 5-HT1A receptor-G protein coupling and leads to heterologous sensitization of adenylate cyclase. In contrast, the effects of short-term (2 h) 5-HT1A receptor activation on subsequent adenylate cyclase activity have not been determined. The present study examined and characterized 5-HT1A receptor-induced heterologous sensitization following short-term activation in CHO-5-HT1A cells. Short-term activation of 5-HT1A receptors with full agonists, as well as the partial agonist, buspirone, markedly enhanced subsequent forskolin-stimulated cyclic AMP accumulation. This heterologous sensitization was evident after 30 min treatment with 5HT and appeared to be near maximal following 2 h agonist treatment. Sensitization was characterized by a dose-dependent increase in forskolin-stimulated cyclic AMP accumulation and was prevented by WAY 100635 or by pertussis toxin treatment. The ability of the 5-HT1A agonists to induce heterologous sensitization was not significantly altered by agents shown previously to modulate 5-HT1A-mediated inhibition of cyclic AMP accumulation.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Adenylyl Cyclases; Animals; Arachidonic Acid; Buspirone; Calcimycin; CHO Cells; Colforsin; Cricetinae; Cricetulus; Cyclic AMP; Cycloheximide; Dose-Response Relationship, Drug; Flavonoids; Humans; Indoles; Indomethacin; Maleimides; Pertussis Toxin; Phorbol Esters; Piperazines; Pyridines; Receptor, Serotonin, 5-HT1A; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Time Factors; Tryptamines