Differential effects of LPS and TGF-beta on the production of IL-6 and IL-12 by Langerhans cells, splenic dendritic cells, and macrophages.
We examined modulatory effects of lipopolysaccharide (LPS) on IL-6 and IL-12 production by mouse Langerhans cells (LC), spleen-derived CD11c+ dendritic cells (DC), and macrophages (Mphi). Low dose LPS (1 ng/ml) increased IL-6 and IL-12 p40 production by Mphi. LPS slightly augmented IL-6 production but showed no effect on IL-12 p40 production by DC. In contrast, only high dose LPS (1 microg/ml) induced IL-6 but not IL-12 p40 production by LC. CD14 expression was the highest on Mphi and then on DC, but not on LC, which may explain the difference in responsiveness to LPS. We also found that TGF-beta inhibited IL-6 and IL-12 p40 production by LPS-stimulated Mphi. However, TGF-beta did not inhibit IL-6 production and even enhanced IL-12 p40 production by anti-CD40/IFN-gamma-stimulated Mphi. Concerning LC, TGF-beta enhanced IL-6 and IL-12 p40 production when stimulated with anti-CD40/IFN-gamma alone or with anti-CD40/IFN-gamma and LPS. Taken together, these findings indicate diverse effects of LPS and TGF-beta on these antigen presenting cells, which probably represents their differential roles in the innate immunity.
Tada
Yayoi
Y
Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Asahina
Akihiko
A
Fujita
Hideki
H
Mitsui
Hiroshi
H
Torii
Hideshi
H
Watanabe
Takahiro
T
Tamaki
Kunihiko
K
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000096:biosynthesis*; D007801:Langerhans Cells / Q000187:drug effects* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D021122:Protein Subunits / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology*
D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D021122:Protein Subunits; D016212:Transforming Growth Factor beta; D018664:Interleukin-12