Role of Cordycepin and Adenosine on the Phenotypic Switch of Macrophages via Induced Anti-inflammatory Cytokines.
BACKGROUND
Chronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine.


METHODS
We confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change.


RESULTS
LPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naïve macrophages, through the treatment with high concentrations of cordycepin (40 microg/ml). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-1beta, TNF-alpha) and chemokines (CX3CR1, RANTES), as well as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-beta) were up-regulated by both cordycepin and adenosine.


CONCLUSIONS
Based on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.
Shin
Seulmee
S
College of Pharmacy, Sahmyook University, Seoul 139-742, Korea.
Moon
Sunhee
S
Park
Yoonhee
Y
Kwon
Jeonghak
J
Lee
Seungjeong
S
Lee
Chong-Kil
CK
Cho
Kyunghae
K
Ha
Nam-Joo
NJ
Kim
Kyungjae
K