PMID- 26791350
OWN - NLM
STAT- MEDLINE
DCOM- 20161219
LR  - 20191210
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 65
IP  - 4
DP  - 2016 Apr
TI  - A novel eremophilane lactone inhibits FcepsilonRI-dependent release of pro-inflammatory 
      mediators: structure-dependent bioactivity.
PG  - 303-11
LID - 10.1007/s00011-016-0917-2 [doi]
AB  - BACKGROUND: Allergic inflammation is primarily mediated by immune effector cells 
      such as mast cells and basophils that release proinflammatory cytokines. Both 
      mast cells and basophils are activated via their high affinity IgE receptor 
      (FcepsilonRI) which initiates the release of proinflammatory mediators such as 
      histamine and tumor necrosis factor (TNF). Considerable effort has been focused 
      on finding an effective basophil stabilizer that inhibits the activation of 
      FcepsilonRI-activated mediator release. Recently, eremophilane lactones, a novel family 
      of sesquiterpene compound originally isolated from Petasites japonicas (Sieb. et 
      Zucc.), have been described, and it has been postulated that they may have 
      anti-inflammatory activity, particularly in allergic disease. OBJECTIVE: Our 
      objective was to determine the effect of two eremophilane lactones derived from 
      6beta-angeloyloxy-3beta,8-dihydroxyeremophil-7(11)-en-12,8beta-olide (F-1) on 
      immunoglobulin E (IgE)-dependent release of pro-inflammatory mediators by a 
      basophil cell line, RBL-2H3, a model system for FcepsilonRI-mediated activation of 
      pro-inflammatory mediator release. METHODS: The parent compound (F-1) was 
      chemically modified to produce F-1a 
      [6beta-angeloyloxy-3beta-benzoyloxy-8-hydroxyeremophil-7(11)-en-12,8beta-olide] and F-1b 
      [6beta-angeloyloxy-3beta,8-diacetoxyeremophil-7(11)-en-12,8beta-olide]. RBL-2H3 cells were 
      sensitized with DNP-specific IgE and then activated with DNP-BSA. The effect of 
      these compounds on IgE-dependent basophil degranulation was assessed by measuring 
      the release of beta-hexosaminidase (b-hex). In addition, TNF release was measured 
      via ELISA. RESULTS: The phenylacetyl reaction modified C-8 and produced F-1a 
      whereas acetylation of F-1 produced F-1b. F-1a was not cytotoxic to RBL-2H3 cells 
      even at 50 muM, but F-1b was slightly cytotoxic at 50 muM, reducing viability of 
      the cells by approximately 15 %. Neither F-1a nor F-1b inhibited FcepsilonRI-dependent 
      activation of RBL-2H3 cells when the cells were pretreated for only 30 min with 
      the compounds. However, 24 h pretreatment with F-1a inhibited antigen-dependent 
      degranulation by as much as 60 % and TNF production by as much as 90 %. F-1b had 
      no effect on RBL-2H3 activation via FcepsilonRI. CONCLUSIONS: These results indicate 
      that F-1a inhibits degranulation of RBL-2H3 cells activated via the high affinity 
      IgE receptor, FcepsilonRI, and that this effect is dependent upon hydroxylation of the 
      third carbon.
FAU - Qian, Fei
AU  - Qian F
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, China.
FAU - Guo, Gujiang
AU  - Guo G
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, China.
FAU - Li, Yiming
AU  - Li Y
AD  - Shanghai University of Traditional Chinese Medicine, Shanghai, China.
FAU - Kulka, M
AU  - Kulka M
AD  - National Institute for Nanotechnology, 11421 Saskatchewan Dr., Edmonton, T6G 2M9, 
      AB, Canada. marianna.kulka@nrc.ca.
LA  - eng
PT  - Journal Article
DEP - 20160120
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Lactones)
RN  - 0 (Polycyclic Sesquiterpenes)
RN  - 0 (Receptors, IgE)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (eremophilane compounds)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
SB  - IM
MH  - Animals
MH  - Cell Degranulation/drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Immunoglobulin E/immunology
MH  - Lactones/chemistry/*pharmacology
MH  - Polycyclic Sesquiterpenes
MH  - Rats
MH  - Receptors, IgE/*immunology
MH  - Sesquiterpenes/chemistry/*pharmacology
MH  - Structure-Activity Relationship
MH  - Tumor Necrosis Factor-alpha/immunology
MH  - beta-N-Acetylhexosaminidases/immunology
OTO - NOTNLM
OT  - Anti-inflammation
OT  - Degranulation
OT  - Mast cell
OT  - Sesquiterpene
OT  - TNF
EDAT- 2016/01/23 06:00
MHDA- 2016/12/20 06:00
CRDT- 2016/01/22 06:00
PHST- 2015/09/03 00:00 [received]
PHST- 2016/01/08 00:00 [accepted]
PHST- 2015/12/21 00:00 [revised]
PHST- 2016/01/22 06:00 [entrez]
PHST- 2016/01/23 06:00 [pubmed]
PHST- 2016/12/20 06:00 [medline]
AID - 10.1007/s00011-016-0917-2 [pii]
AID - 10.1007/s00011-016-0917-2 [doi]
PST - ppublish
SO  - Inflamm Res. 2016 Apr;65(4):303-11. doi: 10.1007/s00011-016-0917-2. Epub 2016 Jan 
      20.