Prostaglandin E(1) protects against liver injury induced by Escherichia coli infection via a dominant Th2-like response of liver T cells in mice.
Prostaglandin E series (PGEs) are known to protect against lipopolysaccharide (LPS)-induced liver injury by down-regulating the production of inflammatory cytokines. We show here a novel mechanism whereby prostaglandin E(1) protects mice against liver injury after Escherichia coli infection. Prostaglandin E(1) administration suppressed circulating interleukin 12 (IL-12) levels but increased the IL-10 production after E. coli challenge. Furthermore, prostaglandin E(1)-alpha-cyclodextrin (PGE(1)) shifted the Th1/Th2 balance of CD3(intermediate) IL-2Rbeta(+) T cells in the liver to a dominant Th2-like response. Neutralization of endogenous IL-4 by administration of anti-IL-4 monoclonal antibody (mAb) diminished the inhibitory effect of prostaglandin E(1) on liver injury after E. coli challenge. These results suggested that the Th2-like response of liver T cells may be at least partly involved in the mechanism whereby prostaglandin E(1) protects against E. coli-induced liver injury.
Mokuno
Y
Y
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan.
Takano
M
M
Matsuguchi
T
T
Nishimura
H
H
Washizu
J
J
Naiki
Y
Y
Nimura
Y
Y
Yoshikai
Y
Y
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal; D003505:Cyclodextrins; D004305:Dose-Response Relationship, Drug; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D005260:Female; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008107:Liver Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D018655:Lymphocyte Count / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D047391:alpha-Cyclodextrins
D000911:Antibodies, Monoclonal; D003505:Cyclodextrins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D047391:alpha-Cyclodextrins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D000527:Alprostadil; C032613:alpha-cyclodextrin