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Induction of interleukin‐12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4 + T cells from a Th2 to a Th1 response
Author(s) -
Kim Tae S.,
Kang Bok Y.,
Cho Daeho,
Kim Seung H.
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01673.x
Subject(s) - berberine , cd80 , cd40 , cd86 , lipopolysaccharide , cytotoxic t cell , biology , antigen , cytokine , microbiology and biotechnology , antigen presenting cell , chemistry , t cell , immune system , immunology , in vitro , biochemistry
Summary In this study we investigated whether berberine‐mediated induction of interleukin‐12 (IL‐12) production in antigen‐presenting cells could regulate a cytokine profile of antigen‐primed CD4 + T helper (Th) cells. Pretreatment with berberine induced IL‐12 production in both macrophages and dendritic cells, and significantly increased the levels of IL‐12 production in lipopolysaccharide‐stimulated macrophages and in CD40 ligand‐stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon‐γ (IFN‐γ) and reduced their ability to induce IL‐4 in antigen‐primed CD4 + T cells. Berberine did not influence the macrophage cell surface expression of the class II major histocompatibility complex molecule, the co‐stimulatory molecules CD80 and CD86, and intracellular adhesion molecule‐1. Addition of neutralizing anti‐IL‐12p40 monoclonal antibody to cultures of berberine‐pretreated macrophages and CD4 + T cells restored IL‐4 production in antigen‐primed CD4 + T cells. The in vivo administration of berberine resulted in the enhanced induction of IL‐12 production by macrophages when stimulated in vitro with lipopolysaccharide or heat‐killed Listeria monocytogenes , leading to the inhibition of the Th type 2 cytokine profile (decreased IL‐4 and increased IFN‐γ production) in antigen‐primed CD4 + T cells. These findings may point to a possible therapeutic use of berberine or medicinal plants containing berberine in the Th type 2 cell‐mediated immune diseases such as allergic diseases.