Impaired IgG production in mice deficient for heat shock transcription factor 1.
Heat shock factor 1 (HSF1) is a major transactivator of heat shock proteins in response to heat shock, and it is also involved in oogenesis, spermatogenesis, and placental development. However, we do not know the molecular mechanisms controlling developmental processes. In this study, we found that HSF1-null mice exhibited a significant decrease in the T cell-dependent B cell response. When mice were immunized intraperitoneally with sheep red blood cells, the sheep red blood cell-specific IgG production, especially IgG2a production, in HSF1-null mice was about 50% lower than that in wild-type mice at 6 days after the immunization, whereas IgM production was normal. The number of bromodeoxyuridine-incorporated spleen cells in immunized HSF1-null mice was one-third that in immunized wild-type mice, indicating reduced proliferation of the spleen cells. We analyzed levels of cytokines and chemokines in spleen cells and in peritoneal macrophages stimulated with lipopolysaccharide and interferon-gamma and found that expression levels of interleukin-6 and CCL5 were significantly lower in HSF1-null cells than those in wild-type cells. Furthermore, we demonstrated that the IL-6 gene is a direct target gene of HSF1. These results revealed a novel molecular link between HSF1 and a gene related to immune response and inflammation.
Inouye
Sachiye
S
Departments of Biochemistry and Molecular Biology and Microbiology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan.
Izu
Hanae
H
Takaki
Eiichi
E
Suzuki
Harumi
H
Shirai
Mutsunori
M
Yokota
Yoshifumi
Y
Ichikawa
Hitoshi
H
Fujimoto
Mitsuaki
M
Nakai
Akira
A
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D018946:Chemokine CCL5; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D019992:Databases as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006720:Homozygote; D007074:Immunoglobulin G / Q000737:chemistry*; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013154:Spleen / Q000166:cytology; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D002843:Chromatin; D004396:Coloring Agents; D016207:Cytokines; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D007074:Immunoglobulin G; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors; D009569:Nitric Oxide; D007371:Interferon-gamma; C022616:thiazolyl blue; D001973:Bromodeoxyuridine