QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.072512v1 312/1/366    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iruretagoyena, M. I. Articles by Kalergis, A. M. Search for Related Content PubMed PubMed Citation Articles by Iruretagoyena, M. I. Articles by Kalergis, A. M.

INFLAMMATION AND IMMUNOPHARMACOLOGY

Andrographolide Interferes with T Cell Activation and Reduces Experimental Autoimmune Encephalomyelitis in the Mouse

Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Chile (M.I.I., J.A.T., P.A.G., S.E.S., C.A.F., A.M.K.); and Instituto de Farmacología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Chile (R.A.B., J.L.H.)

Andrographolide is a bicyclic diterpenoid lactone derived from extracts of Andrographis paniculata, a plant indigenous to South Asian countries that shows anti-inflammatory properties. The molecular and cellular bases for this immunomodulatory capacity remain unknown. Here, we show that andrographolide is able to down-modulate both humoral and cellular adaptive immune responses. In vitro, this molecule was able to interfere with T cell proliferation and cytokine release in response to allogenic stimulation. These results were consistent with the observation that T cell activation by dendritic cells (DCs) was completely abolished by exposing DCs to andrographolide during antigen pulse. This molecule was able to interfere with maturation of DCs and with their ability to present antigens to T cells. Furthermore, in vivo immune responses such as antibody response to a thymus-dependent antigen and delayed-type hypersensitivity were drastically diminished in mice by andrographolide treatment. Finally, the ability of andrographolide to inhibit T cell activation was applied to interfere with the onset of experimental autoimmune encephalomyelitis (EAE), an inflammatory demyelinating disease of the central nervous system that is primarily mediated by CD4⁺ T cells and serves as an animal model for human multiple sclerosis. Treatment with andrographolide was able to significantly reduce EAE symptoms in mice by inhibiting T cell and antibody responses directed to myelin antigens. Our data suggest that andrographolide is able to efficiently block T cell activation in vitro, as well as in vivo, a feature that could be useful for interfering with detrimental T cell responses.

Address correspondence to: Dr. Alexis M. Kalergis, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile. E-mail: kalergis{at}bio.puc.cl

This article has been cited by other articles:

				Z. Bao, S. Guan, C. Cheng, S. Wu, S. H. Wong, D. M. Kemeny, B. P. Leung, and W. S. F. Wong A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-{kappa}B Pathway Am. J. Respir. Crit. Care Med., April 15, 2009; 179(8): 657 - 665. [Abstract] [Full Text] [PDF]

				J. A. Tobar, L. J. Carreno, S. M. Bueno, P. A. Gonzalez, J. E. Mora, S. A. Quezada, and A. M. Kalergis Virulent Salmonella enterica Serovar Typhimurium Evades Adaptive Immunity by Preventing Dendritic Cells from Activating T Cells. Infect. Immun., November 1, 2006; 74(11): 6438 - 6448. [Abstract] [Full Text] [PDF]

				M. I. Iruretagoyena, S. E. Sepulveda, J. P. Lezana, M. Hermoso, M. Bronfman, M. A. Gutierrez, S. H. Jacobelli, and A. M. Kalergis Inhibition of Nuclear Factor-{kappa}B Enhances the Capacity of Immature Dendritic Cells to Induce Antigen-Specific Tolerance in Experimental Autoimmune Encephalomyelitis J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 59 - 67. [Abstract] [Full Text] [PDF]