IL-1 beta regulates the expression of the Gi2 alpha gene via lipid mediators in guinea pig tracheal muscle.
When isolated guinea pig muscle preparations were incubated with human recombinant IL-1 beta, mRNA level of Gi2 alpha but not of Gs alpha increased in a time and dose dependent manner. The increase was partially blocked by inhibitors of lipoxygenase (NDGA) and cyclooxygenase (indomethacin) and PAF antagonist (SC47014A), while U46619 (thromboxane A2 mimetic), LTD4, 15-HETE and PAF partially mimicked it. The IL-1 beta induced Gi2 alpha expression was almost completely inhibited by anti-phospholipase A2 antiserum, whereas preimmune serum had no apparent effects. From these observations, we suggest that IL-1 beta first induces the synthesis and release of Type II inflammatory phospholipase A2, which in turn stimulates the expression of Gi2 alpha gene via production of various lipid mediators.
Hirata
F
F
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202.
Lee
J Y
JY
Sakamoto
T
T
Nomura
A
A
Uchida
Y
Y
Hirata
A
A
Hasegawa
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology; D008055:Lipids / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D006893:Hydroxyeicosatetraenoic Acids; D007375:Interleukin-1; D008055:Lipids; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D011994:Recombinant Proteins; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D017998:Leukotriene D4; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009637:Masoprocol; D019204:GTP-Binding Proteins; D007213:Indomethacin