Kupffer cells may autoregulate interleukin 1 production by producing interleukin 1 inhibitor and prostaglandin E2.
Rat Kupffer cells stimulated with bacterial lipopolysaccharide (LPS) produced high levels of interleukin 1 (IL-1), as determined by thymocyte proliferation assay. Indomethacin revealed a dose-dependent augmentation in IL-1 production, in parallel with a dose-dependent reduction in prostaglandin E2 production by Kupffer cells. The addition of exogenous prostaglandin E2, dibutyryl cAMP, or isoproterenol led to a dose-dependent suppression of IL-1 production. The supernatant from LPS-stimulated Kupffer cells also contained factors that inhibited IL-1-induced thymocyte proliferation. Upon gel filtration, two inhibitory peaks, at apparent MW of 27,000 and 6000, were obtained. The latter but not the former fraction also affected interleukin 2 (IL-2)-induced thymocyte proliferation. Increasing amounts of IL-1 overcame the inhibitory activity derived from the 27,000 MW fractions. These results suggest to us that prostaglandin E2 and IL-1 inhibitor released by Kupffer cells may be involved in negative self-control in regulating IL-1 production and its action.
Shirahama
M
M
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ishibashi
H
H
Tsuchiya
Y
Y
Kurokawa
S
S
Hayashida
K
K
Okumura
Y
Y
Niho
Y
Y
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006706:Homeostasis / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D007728:Kupffer Cells / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects
D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008222:Lymphokines; D003994:Bucladesine; D015232:Dinoprostone; D007545:Isoproterenol; D007213:Indomethacin