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• W2020990519 abstract "We have previously shown that 11‐keto boswellic acids (11‐keto‐BAs), the active principles of Boswellia serrata gum resins, activate p38 MAPK and p42/44 MAPK and stimulate Ca 2+ mobilisation in human polymorphonuclear leucocytes (PMNL). In this study, we attempted to connect the activation of MAPK and mobilisation of Ca 2+ to functional responses of PMNL, including the formation of reactive oxygen species (ROS), release of arachidonic acid (AA), and leukotriene (LT) biosynthesis. 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. Based on inhibitor studies, 11‐keto‐BA‐induced ROS formation is Ca 2+ ‐dependent and is mediated by NADPH oxidase involving PI 3‐K and p42/44 MAPK signalling pathways. Also, the release of AA depends on Ca 2+ and p42/44 MAPK , whereas the pathways stimulating 5‐LO are not readily apparent. Pertussis toxin, which inactivates G i/0 protein subunits, prevents MAPK activation and Ca 2+ mobilisation induced by 11‐keto‐BAs, implying the involvement of a G i/0 protein in BA signalling. 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 Ca 2+ may depend on the cell type or the differentiation status. In summary, we conclude that BAs act via G i/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" @default.
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• W2020990519 date "2004-01-01" @default.
• W2020990519 modified "2023-10-14" @default.
• W2020990519 title "Coupling of boswellic acid-induced Ca²⁺mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes" @default.
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• W2020990519 doi "https://doi.org/10.1038/sj.bjp.0705604" @default.
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