title: CCL22/Macrophage-derived Chemokine Expression in Apolipoprotein E-deficient Mice and Effects of Histamine in the Setting of Atherosclerosis.
abstract: OBJECTIVE
  Macrophage-derived chemokine (CCL22) is a member of the CC-family of chemokines synthesized by monocyte-derived macrophages. Previous studies have reported a relationship between CCL22 and atherosclerosis and the role of histamine in this pathway. Histamine ncreases the CCL22 expression in human monocytes via the H2 receptor. In this study, we investigated the effects of CCL22 and the role of histamine in mouse monocytes with respect to atherosclerosis.
  
  
  RESULTS
  The expression of CCL22 was investigated in apolipoprotein E (apoE)-deficient mice. The mice had high serum concentrations of CCL22 and their atherosclerotic lesions contained abundant levels of CCL22. In addition, when the mouse monocyte cell line (J774A.1 cells) differentiated into macrophage-like cells, the cells showed a similar expression of CCL22 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 CCL22 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 CCL22 expression via the histamine H2 receptor.
  
  
  CONCLUSIONS
  The current results support our previous CCL22 studies in the setting of human atherosclerosis and suggest that this molecule is involved in the atherogenic processes in a mouse model of atherosclerosis.
authors.affiliation: Department of Laboratory and Transfusion Medicine, University of Occupational and Environmental Health.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nabeshima
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Noguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masaru
authors.initials: M
authors.lastname: Harada
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008859:Microscopy, Polarization; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011970:Receptors, Histamine H2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D012333:RNA, Messenger; D011970:Receptors, Histamine H2; D006632:Histamine