Fatty acid-binding protein regulates LPS-induced TNF-alpha production in mast cells.
There has been increasing evidence for the involvement of fatty acid-binding proteins (FABPs) in the cytokine production of macrophages and dendritic cells probably through the control of cellular lipid metabolism and signal transduction. Since mast cells (MCs) are recently shown to be involved in immune response through modification of cytokine production, it is possible that some FABPs could also be involved in the immune response of MCs. In this study, we found that epidermal-type FABP (E-FABP) was expressed in murine bone marrow-derived MCs (BMMCs). Using BMMCs from genetically E-FABP-null mutated mice, we demonstrated that E-FABP in BMMCs plays a key role in the production of TNF-alpha following lipopolysaccharide (LPS) stimulation. In the in vivo septic peritonitis model (cecal ligation and puncture model), E-FABP-null mice showed a significantly increased mortality compared to wild-type mice. However, no significant difference in antigen-induced cytokine production was observed between wild-type and E-FABP-null BMMCs, and systemic anaphylaxis was equally induced in vivo in both wild-type and E-FABP-null mice. These results suggest that E-FABP is specifically involved in the LPS-induced cytokine production of MCs, and could play a role in the host-defense against bacterial infection, possibly through regulation of TNF-alpha production.
Yamamoto
Noriko
N
Department of Organ Anatomy, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami Kogushi, Ube 755-8505, Japan.
Kaneko
Izumi
I
Motohashi
Keiju
K
Sakagami
Hiroyuki
H
Adachi
Yasuhiro
Y
Tokuda
Nobuko
N
Sawada
Tomoo
T
Furukawa
Hiroshi
H
Ueyama
Yoshiya
Y
Fukunaga
Kohji
K
Ono
Masao
M
Kondo
Hisatake
H
Owada
Yuji
Y
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010538:Peritonitis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000276:immunology*; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D050556:Fatty Acid-Binding Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha