Aim: Macrophage-derived chemokine (CCL
22
) is a member of the CC-family of chemokines synthesized by monocyte-derived macrophages. Previous studies have reported a relationship between CCL
22
and atherosclerosis and the role of histamine in this pathway. Histamine ncreases the CCL
22
expression in human monocytes via the H2 receptor. In this study, we investigated the effects of CCL
22
and the role of histamine in mouse monocytes with respect to atherosclerosis.
Methods and Results: The expression of CCL
22
was investigated in apolipoprotein E (apoE)-deficient mice. The mice had high serum concentrations of CCL
22
and their atherosclerotic lesions contained abundant levels of CCL
22
. In addition, when the mouse monocyte cell line (J774A.1 cells) differentiated into macrophage-like cells, the cells showed a similar expression of CCL
22
and reduced expression of H2 receptors. Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) in a single enzymatic step. HDC knockout mice were compared with apoE/HDC double knockout mice. The findings indicated that the expression of CCL
22
in atherosclerosis models is under the influence of histamine. In addition,
in vitro studies using J774A.1 cells and an
in vivo study using histamine receptor knockout mice showed that histamine stimulates the CCL
22
expression via the histamine H2 receptor.
Conclusions: The current results support our previous CCL
22
studies in the setting of human atherosclerosis and suggest that this molecule is involved in the atherogenic processes in a mouse model of atherosclerosis.
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