title: 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.
abstract: 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.
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Szigony u. 43, Hungary.
authors.forename: C
authors.initials: C
authors.lastname: Csölle
authors.forename: B
authors.initials: B
authors.lastname: Sperlágh
mesh_terms: 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
chemical_list: 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