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- Title
Coupling of boswellic acid-induced Ca<sup>2+</sup> mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes.
- Authors
Altmann, Anja; Poeckel, Daniel; Fischer, Lutz; Schubert-Zsilavecz, Manfred; Steinhilber, Dieter; Werz, Oliver
- Abstract
1: We have previously shown that 11-keto boswellic acids (11-keto-BAs), the active principles of Boswellia serrata gum resins, activate p38 MAPK and p42/44MAPK and stimulate Ca2+ mobilisation in human polymorphonuclear leucocytes (PMNL). 2: In this study, we attempted to connect the activation of MAPK and mobilisation of Ca2+ to functional responses of PMNL, including the formation of reactive oxygen species (ROS), release of arachidonic acid (AA), and leukotriene (LT) biosynthesis. 3: We found that, in PMNL, 11-keto-BAs stimulate the formation of ROS and cause release of AA as well as its transformation to LTs via 5-lipoxygenase. 4: Based on inhibitor studies, 11-keto-BA-induced ROS formation is Ca2+-dependent and is mediated by NADPH oxidase involving PI 3-K and p42/44MAPK signalling pathways. Also, the release of AA depends on Ca2+ and p42/44MAPK, whereas the pathways stimulating 5-LO are not readily apparent. 5: Pertussis toxin, which inactivates Gi/0 protein subunits, prevents MAPK activation and Ca2+ mobilisation induced by 11-keto-BAs, implying the involvement of a Gi/0 protein in BA signalling. 6: Expanding studies on differentiated haematopoietic cell lines (HL60, Mono Mac 6, BL41-E-95-A) demonstrate that the ability of BAs to activate MAPK and to mobilise Ca2+ may depend on the cell type or the differentiation status. 7: In summary, we conclude that BAs act via Gi/0 protein(s) stimulating signalling pathways that control functional leucocyte responses, in a similar way as chemoattractants, that is, N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor.British Journal of Pharmacology (2004) 141, 223-232. doi:10.1038/sj.bjp.0705604
- Subjects
NEUTROPHILS; LEUCOCYTES; REACTIVE oxygen species; LIPOXYGENASES; ARACHIDONIC acid; LIPID metabolism; PEROXIDES
- Publication
British Journal of Pharmacology, 2004, Vol 141, Issue 2, p223
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705604