PMID- 24920235 OWN - NLM STAT- MEDLINE DCOM- 20150407 LR - 20220318 IS - 1744-5116 (Electronic) IS - 1388-0209 (Linking) VI - 52 IP - 7 DP - 2014 Jul TI - Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-kappaB signaling in activated HMC-1 human mast cells. PG - 926-32 LID - 10.3109/13880209.2013.865243 [doi] AB - CONTEXT: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown. OBJECTIVE: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro. MATERIALS AND METHODS: To investigate the bioactive potential of CAPE (10 or 20 microM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used. RESULTS: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 microM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1beta (4.775 versus 0.713 pg/ml, IC50 = 6.67 microM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 microM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 microM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-kappaB activation by suppressing IkappaBalpha phosphorylation and its degradation. DISCUSSION AND CONCLUSION: Our results indicated that CAPE can modulate mast cell-mediated allergic disease. FAU - Cho, Mi Suk AU - Cho MS AD - Department of Dental Hygiene, Choonhae College of Health Sciences , Ulsan , Republic of Korea . FAU - Park, Won Sun AU - Park WS FAU - Jung, Won-Kyo AU - Jung WK FAU - Qian, Zhong-Ji AU - Qian ZJ FAU - Lee, Dae-Sung AU - Lee DS FAU - Choi, Jung-Sik AU - Choi JS FAU - Lee, Da-Young AU - Lee DY FAU - Park, Sae-Gwang AU - Park SG FAU - Seo, Su-Kil AU - Seo SK FAU - Kim, Hak-Ju AU - Kim HJ FAU - Won, Jun Yeon AU - Won JY FAU - Yu, Byeng Chul AU - Yu BC FAU - Choi, Il-Whan AU - Choi IW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Pharm Biol JT - Pharmaceutical biology JID - 9812552 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Caffeic Acids) RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 37341-29-0 (Immunoglobulin E) RN - 820484N8I3 (Histamine) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - G960R9S5SK (caffeic acid phenethyl ester) RN - ML9LGA7468 (Phenylethyl Alcohol) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Caffeic Acids/*pharmacology MH - Calcium/metabolism MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cytokines/drug effects MH - Histamine/metabolism MH - Histamine Release/drug effects MH - Humans MH - Hypersensitivity/prevention & control MH - Immunoglobulin E/metabolism MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Mast Cells/cytology/*drug effects/metabolism MH - Mice MH - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism MH - NF-kappa B/*antagonists & inhibitors/metabolism MH - Phenylethyl Alcohol/*analogs & derivatives/pharmacology MH - Phosphorylation/drug effects OTO - NOTNLM OT - Allergy OT - cytokine OT - histamine OT - immunoglobulin E OT - passive cutaneous anaphylaxis EDAT- 2014/06/13 06:00 MHDA- 2015/04/08 06:00 CRDT- 2014/06/13 06:00 PHST- 2014/06/13 06:00 [entrez] PHST- 2014/06/13 06:00 [pubmed] PHST- 2015/04/08 06:00 [medline] AID - 10.3109/13880209.2013.865243 [doi] PST - ppublish SO - Pharm Biol. 2014 Jul;52(7):926-32. doi: 10.3109/13880209.2013.865243.