Melatonin, which is the main product of the
pineal gland, has well documented
antioxidant and immune-modulatory effects.
Macrophages produce molecules that are known to
play roles in inflammatory responses. We conducted
microarray analysis to evaluate the global
gene expression profiles in response to
treatment with
melatonin in
lipopolysaccharide (LPS) activated RAW 264.7
macrophage cells. In addition, eight
genes were subjected to real-
time reverse transcription polymerase chain reaction (RT-PCR) to confirm the results of the microarray. The
cells were treated with LPS or
melatonin plus LPS for 24 hr. LPS induced the
up-regulation of 1073
genes and the
down-regulation of 1144
genes when compared to the
control group.
Melatonin pretreatment of LPS-stimulated
RAW 264.7 cells resulted in the
down regulation of 241
genes and
up regulation of 164
genes. Interestingly, among
genes related to
macrophage-mediated
immunity, LPS increased the expression of seven
genes (Adora2b, Fcgr2b, Cish, Cxcl10, Clec4n, Il1a, and Il1b) and decreased the expression of one
gene (Clec4a3). These changes in expression were attenuated by
melatonin. Furthermore, the results of
real-time PCR were
similar to those of the microarray. Taken together, these results suggest that
melatonin may have a suppressive effect on LPS-induced expression of
genes involved in the
regulation of
immunity and defense in RAW 264.7
macrophage cells. Moreover, these results may explain beneficial effects of
melatonin in the
treatment of various inflammatory conditions.