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

J Neuroimmunol. 2010 Feb 26;219(1-2):38-46. doi: 10.1016/j.jneuroim.2009.11.011. Epub 2009 Dec 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Analysis of Variance
  • Animals
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gene Expression Regulation / drug effects*
  • Hippocampus / drug effects*
  • Imidazoles / pharmacology
  • Interleukin-1beta / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Purinergic P2 Receptor Antagonists
  • Pyridines / pharmacology
  • Pyridoxal Phosphate / analogs & derivatives
  • Pyridoxal Phosphate / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic P2 / deficiency
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X7
  • Xanthines / pharmacology

Substances

  • Cytokines
  • Enzyme Inhibitors
  • Imidazoles
  • Interleukin-1beta
  • Lipopolysaccharides
  • P2rx7 protein, mouse
  • Purinergic P2 Receptor Antagonists
  • Pyridines
  • RNA, Messenger
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Xanthines
  • pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
  • 3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate
  • Pyridoxal Phosphate
  • Adenosine Triphosphate
  • 1,3-dipropyl-8-cyclopentylxanthine
  • SB 203580