Mechanism of up-regulation of immunoglobulin A production in the intestine of mice unresponsive to lipopolysaccharide.
The mechanisms by which immunoglobulin A (IgA) production up-regulates in the intestine of Toll-like receptor-4 (TLR4)-mutated mice were investigated. When TLR4-mutated, C3H/HeJ and BALB/lps(d) mice received oral administration of cholera toxin (CT), not only CT-specific IgA levels in the intestinal lavage but also the number of IgA-producing cells in intestinal lamina propria (iLP) significantly increased compared with those of the wild-type C3H/He and BALB/c mice. Interleukin (IL)-5-producing cells and CD86+ cells in iLP also significantly increased in C3H/HeJ mice. The expression of major histocompatibility complex class II and CD86 on cells present in Peyer's patches (PPs) of C3H/HeJ mice was higher than those of C3H/He mice. In non-immunized C3H/HeJ mice, the expression of transforming growth factor-beta (TGF-beta) mRNA and the percentages of IL-10-producing cells in PPs but not in spleen increased when compared with those in C3H/He mice. The suppressor of cytokine signalling-1 (SOCS-1) was expressed in PPs of C3H/He mice but not C3H/HeJ mice. These results indicate that high IgA levels in the intestine of TLR4-mutated mice are due to up-regulation of TGF-beta and IL-10 and the lack of regulation by SOCS-1.
Kaneko
Masahiro
M
Department of Biosciences, School of Science and Graduate School for Fundamental Life Science, Kitasato University, Kanagawa, Japan.
Akiyama
Yoshiyuki
Y
Takimoto
Hiroaki
H
Kumazawa
Yoshio
Y
D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007421:Intestine, Small / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009154:Mutation; D010581:Peyer's Patches / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4