title: Involvement of p38 mitogen-activated protein kinase in the induction of interleukin-12 p40 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid.
abstract: Interleukin (IL)-12 plays a pivotal role in the development of T helper type 1 (Th1)-immune response, which may have therapeutic effects on diseases associated with pathologic Th2 responses such as allergic disorders and asthma. In this study, we investigated the effects of berberine, a benzodioxoloquinolizine alkaloid with anti-microbial and anti-tumor activities, on the production of IL-12 p40, an inducible subunit of IL-12, in mouse macrophages. Berberine-induced IL-12 p40 production and activation of p38 mitogen-activated protein kinase (MAPK) in dose-dependent manners, which were significantly inhibited by p38 MAPK inhibitors and yohimbine, indicating that p38 MAPK and alpha(2)-adrenergic receptor were involved in the induction of IL-12 p40 production in mouse macrophages by berberine. Furthermore, berberine significantly enhanced IL-12 p40 production in mouse macrophages when combined with lipopolysaccharide, a well-known inducer of IL-12 production. These findings may explain some of the known biological effects of berberine and suggests berberine as an immunotherapeutic compound for induction of IL-12, which is potentially applicable for tumors, infectious disease, and airway inflammation.
authors.affiliation: Immunology Laboratory, Research Institute of Drug Development, College of Pharmacy, Chonnam National University, Kwangju 500-757, South Korea.
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
authors.forename: Su Wol
authors.initials: SW
authors.lastname: Chung
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D021122:Protein Subunits; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000470:Alkaloids; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D018341:Receptors, Adrenergic, alpha-2; D001599:Berberine; D018664:Interleukin-12; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases