Complex array of cytokines released by vasoactive intestinal peptide
| Autor: | Janet Hauser, Catherine Y. Spong, Terry M. Phillips, Douglas E. Brenneman, Joanna M. Hill, Illana Gozes |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Macrophage colony-stimulating factor
medicine.medical_specialty medicine.medical_treatment Vasoactive intestinal peptide Adenylate kinase Neuropeptide Biology Cyclase Cellular and Molecular Neuroscience Endocrinology Internal medicine medicine Animals Receptor Cells Cultured Endocrine and Autonomic Systems Macrophage Colony-Stimulating Factor Neuropeptides Granulocyte-Macrophage Colony-Stimulating Factor General Medicine Rats Kinetics medicine.anatomical_structure Cytokine Neurology Animals Newborn Astrocytes Cytokines Pituitary Adenylate Cyclase-Activating Polypeptide Interleukin-3 Neuroglia hormones hormone substitutes and hormone antagonists Astrocyte Adenylyl Cyclases Vasoactive Intestinal Peptide |
| Zdroj: | Neuropeptides. 37(2) |
| ISSN: | 0143-4179 |
| Popis: | A complex mixture of five cytokines has been shown to be released by vasoactive intestinal peptide (VIP). Cytokines were measured in paired samples of culture medium and astroglial cytosol by capillary electrophoresis. This is the first description of VIP-mediated release for TNF-alpha, IL-3, G-CSF and M-CSF from astrocyte cultures. Kinetic studies after VIP treatment demonstrated a gradual but incomplete depletion of cytosolic cytokine levels, with differences observed among the cytokines. Significant increases in release were apparent within 15-30 min for all cytokines. As the recognized VIP receptors (VPAC1 and VPAC2) are linked to adenylate cyclase and also interact with pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), both this homologous peptide and 8-bromo cAMP were investigated and compared to VIP-mediated release. Treatment with 1 mM 8-bromo cAMP produced cytokine release similar in amount to 0.1 nM PACAP-38, but significantly less (50%) in comparison to 0.1 nM VIP. PACAP-38 and VIP exhibited similar EC(50)'s for the release of G-CSF and TNF-alpha; however, the maximal release was 4-6 times greater for VIP than for PACAP-38. This similarity in potency suggested a VPAC-like receptor; however, the greater efficacy for VIP in comparison to PACAP-38, combined with a lack of cAMP production at subnanomolar concentrations of VIP, suggested a mechanism not currently associated with VPAC receptors. For M-CSF, IL-3 and IL-6, the EC(50)'s of VIP were 3-30 times more potent than those of PACAP-38 in producing release. These studies suggested that multiple mechanisms mediate cytokine release in astrocytes: (1) a low efficacy release produced by PACAP-38 that is cAMP-mediated and (2) a high efficacy, VIP-preferring mechanism that was not linked to cAMP. In summary, subnanomolar concentrations of VIP released a complex array of cytokines from astrocytes that may contribute to the mitogenic and neurotrophic properties of this neuropeptide in the central nervous system. |
| Databáze: | OpenAIRE |
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