TY - JOUR
T1 - CDNA microarray analysis of lactoferrin expression in non-neoplastic human hepatocyte PH5CH8 cells
AU - Tamura, Takahiko
AU - Nozaki, Akito
AU - Abe, Ken Ichi
AU - Dansako, Hiromichi
AU - Naka, Kazuhito
AU - Ikeda, Masanori
AU - Tanaka, Katsuaki
AU - Kato, Nobuyuki
N1 - Funding Information:
We thank T. Nakamura for his helpful experimental assistance. This work was supported by Grants-in-Aid for Scientific Research from the Organization for Pharmaceutical Safety and Research (OPSR).
PY - 2005/1/19
Y1 - 2005/1/19
N2 - Lactoferrin (LF), a milk protein belonging to the iron transporter transferrin family, is known as a primary defense protein against pathogenic microorganisms. Previously, we found that bovine and human LFs prevented hepatitis C virus infection in cultured human hepatocytes by a direct interaction with the virus. Since LF is proposed to have transcriptional regulatory activity in addition to its antimicrobial function, we sought to identify the target genes that these two types of LF have in common. To this end, we were the first to perform microarray analysis (9970 genes) using human hepatocytes that expressed bovine or human LF by retrovirus-mediated gene transfer. In the results, LF could give a variety of expression profiles in the human hepatocytes, and showed that 9 and 19 genes were commonly up-regulated (more than 2.0-fold) and down-regulated (less than 0.50-fold), respectively, in both bovine and human LF-expressing cells compared with control cells. Among these genes, we found that γ-aminobutyric acid (GABA)-B receptor 2 was transcriptionally down-regulated by bovine and human LFs, but not by human transferrin. Furthermore, we obtained the suggestive result that LF may modulate the level of intracellular cAMP. This modulation is one of the cellular responses that the GABA-B receptor modifies. This is the first report of microarray analysis applied to search inclusively for the target genes of LF.
AB - Lactoferrin (LF), a milk protein belonging to the iron transporter transferrin family, is known as a primary defense protein against pathogenic microorganisms. Previously, we found that bovine and human LFs prevented hepatitis C virus infection in cultured human hepatocytes by a direct interaction with the virus. Since LF is proposed to have transcriptional regulatory activity in addition to its antimicrobial function, we sought to identify the target genes that these two types of LF have in common. To this end, we were the first to perform microarray analysis (9970 genes) using human hepatocytes that expressed bovine or human LF by retrovirus-mediated gene transfer. In the results, LF could give a variety of expression profiles in the human hepatocytes, and showed that 9 and 19 genes were commonly up-regulated (more than 2.0-fold) and down-regulated (less than 0.50-fold), respectively, in both bovine and human LF-expressing cells compared with control cells. Among these genes, we found that γ-aminobutyric acid (GABA)-B receptor 2 was transcriptionally down-regulated by bovine and human LFs, but not by human transferrin. Furthermore, we obtained the suggestive result that LF may modulate the level of intracellular cAMP. This modulation is one of the cellular responses that the GABA-B receptor modifies. This is the first report of microarray analysis applied to search inclusively for the target genes of LF.
KW - GABA-B receptor
KW - Hepatitis C virus
KW - Lactoferrin
KW - Microarray
KW - PH5CH8
KW - cAMP
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U2 - 10.1016/j.bbagen.2004.10.003
DO - 10.1016/j.bbagen.2004.10.003
M3 - Article
C2 - 15652181
AN - SCOPUS:11844295353
SN - 0304-4165
VL - 1721
SP - 73
EP - 80
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 1-3
ER -
