Peripheral origin of IL-1beta production in the rodent hippocampus under in vivo systemic bacterial lipopolysaccharide (LPS) challenge and its regulation by P2X(7) receptors.
In this study we showed that in vivo bacterial lipopolysaccharide (LPS) challenge elevated IL-1beta level in the rodent hippocampus. Antagonists of P2X receptors inhibited LPS-induced IL-1beta level with a pharmacological profile similar to that of P2X(7)R and their inhibitory effect was attenuated in the absence of P2X(7)R. In wild-type mice, LPS overexpressed mRNA encoding P2X(4) and P2X(7) receptors in the hippocampus and caused also a remarkable increase in the levels of IL-1beta in the serum. The hippocampal increase of IL-1beta has substantially alleviated when contamination of circulating blood cells was excluded by transcardial perfusion, indicating the peripheral origin of hippocampal IL-1beta elevation. These results point to the key role of the endogenous activation of peripheral P2X(7)R in the level of IL-1beta in rodent hippocampus under systemic bacterial endotoxin challenge.
Csölle
C
C
Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Szigony u. 43, Hungary.
Sperlágh
B
B
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D014970:Xanthines / Q000494:pharmacology
D016207:Cytokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C546469:P2rx7 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D014970:Xanthines; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; C093642:SB 203580