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 p42/44(MAPK) and stimulate Ca(2+) mobilisation in human polymorphonuclear leucocytes (PMNL). 2. 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. 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 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. 5. 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. 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 Ca(2+) may depend on the cell type or the differentiation status. 7. 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.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Altmann A,Poeckel D,Fischer L,Schubert-Zsilavecz M,Steinhilber D,Werz Odoi
10.1038/sj.bjp.0705604subject
Has Abstractpub_date
2004-01-01 00:00:00pages
223-32issue
2eissn
0007-1188issn
1476-5381pii
sj.bjp.0705604journal_volume
141pub_type
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journal_title：British journal of pharmacology
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