IL-1 beta potentiates heat-activated currents in rat sensory neurons: involvement of IL-1RI, tyrosine kinase, and protein kinase C.
Interleukin 1 beta (IL-1 beta) is a proinflammatory cytokine that maintains thermal hyperalgesia and facilitates the release of calcitonin gene-related peptide from rat cutaneous nociceptors in vivo and in vitro. Brief applications of IL-1 beta to nociceptive neurons yielded a potentiation of heat-activated inward currents (Iheat) and a shift of activation threshold toward lower temperature without altering intracellular calcium levels. The IL-1 beta-induced heat sensitization was not dependent on G-protein-coupled receptors but was mediated by activation of protein kinases. The nonspecific protein kinase inhibitor staurosporine, the specific protein kinase C inhibitor bisindolylmaleimide BIM1, and the protein tyrosine kinase inhibitor genistein reduced the sensitizing effect of IL-1 beta whereas negative controls were ineffective. RT-PCR and in situ hybridization revealed IL-1RI but not RII expression in neurons rather than surrounding satellite cells in rat dorsal root ganglia. IL-1 beta acts on sensory neurons to increase their susceptibility for noxious heat via an IL-1RI/PTK/PKC-dependent mechanism.
Obreja
Otilia
O
Institut fuer Physiologie und Experimentelle Pathophysiologie, Friedrich-Alexander Universitaet, 91054 Erlangen, Germany.
Rathee
Parvinder K
PK
Lips
Kathrin S
KS
Distler
Carsten
C
Kress
Michaela
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D019833:Genistein / Q000494:pharmacology; D006358:Hot Temperature; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000502:physiology; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D019311:Staurosporine / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D007211:Indoles; D007375:Interleukin-1; D008301:Maleimides; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D053574:Receptors, Interleukin-1 Type II; D013498:Suramin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine; C070515:bisindolylmaleimide I; D002118:Calcium