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Boswellic Acids Activate p42MAPK and p38 MAPK and Stimulate Ca2+ Mobilization,☆☆

https://doi.org/10.1006/bbrc.2001.6153Get rights and content

Abstract

Here we show that extracts of Boswellia serrata gum resins and its constituents, the boswellic acids (BAs), activate the mitogen-activated protein kinases (MAPK) p42MAPK and p38 in isolated human polymorphonuclear leukocytes (PMNL). MAPK activation was rapid and transient with maximal activation after 1–2.5 min of exposure and occurred in a dose-dependent manner. The keto-BAs (11-keto-β-BA and 3-O-acetyl-11-β-keto-BA) gave substantial kinase activation at 30 μM, whereas other BAs lacking the 11-keto group were less effective. Moreover, 11-keto-BAs induced rapid and prominent mobilization of free Ca2+ in PMNL. Inhibitor studies revealed that phosphatidylinositol 3-kinase (PI 3-K) is involved in BA-induced MAPK activation, whereas a minor role was apparent for protein kinase C. MAPK activation by 3-O-acetyl-11-β-keto-BA was partially inhibited when Ca2+ was removed by chelation. Our results suggest that 11-keto-BAs might function as potent activators of PMNL by stimulation of MAPK and mobilization of intracellular Ca2+.

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    This study was supported by grants from the EU (QLG1-CT-2001-01521).

    ☆☆

    Abbreviations used: AB, antibody; A-β-BA, 3-O-acetyl-β-boswellic acid; AKBA, 3-O-acetyl-11-keto-β-boswellic acid; KBA, 11-keto-β-boswellic acid; β-BA, β-boswellic acid; fMLP, N-formyl-methionyl-leucyl-phenylalanine; JNK, c-jun NH2-terminal kinase; MAPK, mitogen-activated protein kinase; MBP, myelin basic protein; MEK, MAPK kinase; PAF, platelet-activating factor; PBS, phosphate-buffered saline, pH 7.4; PG buffer, PBS containing 1 mg/ml glucose; PGC buffer, PBS containing 1 mg/ml glucose and 1 mM CaCl2; PI 3-K, phosphatidylinositol 3-kinase; PKC, protein kinase C; PMNL, polymorphonuclear leukocytes; SDS-b, 2× SDS–PAGE sample loading buffer; WB, Western blotting.

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    To whom correspondence and reprint requests should be addressed at Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, D-60439 Frankfurt, Germany. Fax: +69-798 29323. E-mail: [email protected].

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