Abstract
Aim:
To investigate the immunomodulatory effects of andrographolide on both innate and adaptive immune responses.
Methods:
Andrographolide (10 μg/mL in vitro or 1 mg/kg in vivo) was used to modulate LPS-induced classical activated (M1) or IL-4-induced alternative activated (M2) macrophages in vitro and humor immune response to HBsAg in vivo. Cytokine gene expression profile (M1 vs M2) was measured by real-time PCR, IL-12/IL-10 level was detected by ELISA, and surface antigen expression was evaluated by flow cytometry, whereas phosphorylation level of ERK 1/2 and AKT was determined by Western blot. The level of anti-HBs antibodies in HBsAg immunized mice was detected by ELISA, and the number of HBsAg specific IL-4-producing splenocyte was enumerated by ELISPOT.
Results:
Andrographolide treatment in vitro attenuated either LPS or IL-4 induced macrophage activation, inhibited both M1 and M2 cytokines expression and decreased IL-12/IL-10 ratio (the ratio of M1/M2 polarization). Andrographolide down-regulated the expression of mannose receptor (CD206) in IL-4 induced macrophages and major histocompability complex/costimulatory molecules (MHC I, CD40, CD80, CD86) in LPS-induced macrophages. Correspondingly, anti-HBs antibody production and the number of IL-4-producing splenocytes were reduced by in vivo administration of andrographolide. Reduced phosphorylation levels of ERK1/2 and AKT were observed in macrophages treated with andrographolide.
Conclusion:
Andrographolide can modulate the innate and adaptive immune responses by regulating macrophage phenotypic polarization and Ag-specific antibody production. MAPK and PI3K signaling pathways may participate in the mechanisms of andrographolide regulating macrophage activation and polarization.
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Acknowledgements
This work was supported by the Program of Ministry of Science and Technology of China (S2010GR0385, 2008ZX10004-014, and 2008ZX10002-002), the International Science and Technology Cooperation Program of Shanghai Science and Technology Commission (074307038) and PhD student visiting scholarship of Fudan University for 2008–2009.
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Wang, W., Wang, J., Dong, Sf. et al. Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response. Acta Pharmacol Sin 31, 191–201 (2010). https://doi.org/10.1038/aps.2009.205
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DOI: https://doi.org/10.1038/aps.2009.205
