Potential interaction between CCR1 and its ligand, CCL3, induced by endogenously produced interleukin-1 in human hepatomas.
Hepatoma cell lines can produce a massive amount of chemokines in response to various stimuli including hepatitis viruses and their products. However, it remains elusive on the types of chemokine receptor(s) expressed in the hepatoma tissues and its roles in hepatoma development. To clarify these points, we examined the chemokine receptor expression in six human hepatoma cell lines. All of the hepatoma cell lines constitutively and exclusively expressed CCR1 mRNA and its protein on their cell surface. CCR1 expression was also detected on hepatoma cells and to a lesser degree, on endothelial cells in hepatoma tissues but not in normal liver tissues. Furthermore, CCL3 expression was detected in hepatoma cells, endothelial cells, and to a lesser degree, fibroblast-like cells in hepatoma tissue, whereas only occasional vascular endothelial cells and inflammatory cells in normal liver tissues were weakly positive for CCL3. Moreover, the forskolin-mediated increases in intracellular cAMP concentrations were inhibited by the ligands for CCR1, CCL3, CCL4, and CCL5, suggesting that the expressed CCR1 was functional. Four hepatoma cell lines produced CCL3 only in response to interleukin (IL)-1 alpha and IL-1 beta. Finally, IL-1 alpha and IL-1 beta were detected abundantly in hepatoma tissues but not in normal liver tissues. Thus, IL-1 may enhance the local production of CCL3, which may interact with CCR1 expressed on hepatoma cells, in an autocrine and/or paracrine manner.
Lu
Peirong
P
Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Nakamoto
Yasunari
Y
Nemoto-Sasaki
Yoko
Y
Fujii
Chifumi
C
Wang
Hui
H
Hashii
Minako
M
Ohmoto
Yasukazu
Y
Kaneko
Shuichi
S
Kobayashi
Kenichi
K
Mukaida
Naofumi
N
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C515300:CCR1 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054389:Receptors, CCR1; D019707:Receptors, Chemokine