Acetylcorynoline impairs the maturation of mouse bone marrow-derived dendritic cells via suppression of IκB kinase and mitogen-activated protein kinase activities.

Abstract

BACKGROUND:

Dendritic cells (DCs) are major modulators in the immune system. One active field of research is the manipulation of DCs as pharmacological targets to screen novel biological modifiers for the treatment of inflammatory and autoimmune disorders. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana herbs. We assessed the capability of acetylcorynoline to regulate lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs.

METHODOLOGY/PRINCIPAL FINDINGS:

Our experimental data showed that treatment with up to 20 µM acetylcorynoline does not cause cytotoxicity in cells. Acetylcorynoline significantly inhibited the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also decreased by acetylcorynoline, and the endocytic capacity of LPS-stimulated DCs was restored by acetylcorynoline. In addition, LPS-stimulated DC-elicited allogeneic T-cell proliferation was blocked by acetylcorynoline, and the migratory ability of LPS-stimulated DCs was reduced by acetylcorynoline. Moreover, acetylcorynoline significantly inhibits LPS-induced activation of IκB kinase and mitogen-activated protein kinase. Importantly, administration of acetylcorynoline significantly attenuates 2,4-dinitro-1-fluorobenzene-induced delayed-type hypersensitivity.

CONCLUSIONS/SIGNIFICANCE:

Acetylcorynoline may be one of the potent immunosuppressive agents through the blockage of DC maturation and function.

• Authors: Ru-Huei Fu, Yu-Chi Wang, Shih-Ping Liu, Ching-Liang Chu, Rong-Tzong Tsai, Yu-Chen Ho, Wen-Lin Chang, Shao-Chih Chiu, Horng-Jyh Harn, Woei-Cherng Shyu, Shinn-Zong Lin
• Journal: PloS one (PLoS One) Vol. 8 Issue 3 Pg. e58398 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23472193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Berberine Alkaloids
• Interleukin-6
• Lipopolysaccharides
• Plant Extracts
• Tumor Necrosis Factor-alpha
• acetylcorynoline
• Interleukin-12
• I-kappa B Kinase
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Berberine Alkaloids (pharmacology)
• Bone Marrow Cells (cytology, drug effects)
• Cell Membrane (metabolism)
• Cell Movement
• Cell Survival
• Corydalis (metabolism)
• Dendritic Cells (cytology, drug effects, metabolism)
• Endocytosis
• I-kappa B Kinase (metabolism)
• Inflammation
• Interleukin-12 (metabolism)
• Interleukin-6 (metabolism)
• Lipopolysaccharides (pharmacology)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• Plant Extracts (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)