Mechanism of eosinophil induced signaling in cholinergic IMR-32 cells.
Eosinophils interact with nerve cells, leading to changes in neurotransmitter release, altered nerve growth, and protection from cytokine-induced apoptosis. In part, these interactions occur as a result of activation of neural nuclear factor (NF)-kappaB, which is activated by adhesion of eosinophils to neural intercellular adhesion molecule-1 (ICAM-1). The mechanism and consequence of signaling after eosinophil adhesion to nerve cells were investigated. Eosinophil membranes, which contain eosinophil adhesion molecules but not other eosinophil products, were coincubated with IMR-32 cholinergic nerve cells. The studies showed that there were two mechanisms of activation of NF-kappaB, one of which was dependent on reactive oxygen species, since it was inhibited with diphenyleneiodonium. This occurred at least 30 min after coculture of eosinophils and nerves. An earlier phase of NF-kappaB activation occurred within 2 min of eosinophil adhesion and was mediated by tyrosine kinase-dependent phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1). Coimmunoprecipitation experiments showed that both extracellular signal-regulated kinase 1/2 and IRAK-1 were recruited to ICAM-1 rapidly after coculture with eosinophil membranes. This was accompanied by an induction of ICAM-1, which was mediated by an IRAK-1-dependent pathway. These data indicate that adhesion of eosinophils to IMR-32 nerves via ICAM-1 leads to important signaling events, mediated via IRAK-1, and these in turn lead to expression of adhesion molecules.
Department of Medicine, RCSI, Beaumont Hospital, Dublin 9, Ireland.
David R
DR
Curran
Ross K
RK
Morgan
Paul J
PJ
Kingham
Niamh
N
Durcan
W Graham
WG
McLean
Marie Therese
MT
Walsh
Richard W
RW
Costello
D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002799:Cholinergic Fibers; D018920:Coculture Techniques; D004804:Eosinophils / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation
D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D053592:Interleukin-1 Receptor-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases