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Complex array of cytokines released by vasoactive intestinal peptide
Douglas E Brenneman1, Terry M Phillips, Janet Hauser
1Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. dbrennem@prdus.jnj.com
Neuropeptides
|May 16, 2003
Summary
Vasoactive intestinal peptide (VIP) triggers the release of multiple cytokines from astrocytes, including TNF-alpha, IL-3, G-CSF, and M-CSF. This VIP-induced cytokine release involves distinct mechanisms, some not directly linked to cAMP signaling.
Area of Science:
- Neuroimmunology
- Cellular Signaling
- Cytokine Biology
Background:
- Vasoactive intestinal peptide (VIP) is known to influence various cellular functions.
- Cytokines play crucial roles in the central nervous system, mediating immune responses and neuronal function.
- Astrocyte-derived cytokines are implicated in neuroinflammation and neuroprotection.
Purpose of the Study:
- To investigate the release of cytokines from astrocytes induced by VIP.
- To characterize the signaling mechanisms underlying VIP-mediated cytokine release, comparing it with pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) and cAMP.
- To explore the potential contribution of VIP-induced cytokine release to its neurotrophic and mitogenic effects.
Main Methods:
- Measurement of five cytokines (TNF-alpha, IL-3, G-CSF, M-CSF, IL-6) in astrocyte culture medium and cytosol using capillary electrophoresis.
- Kinetic analysis of cytokine release following VIP treatment.
- Comparison of VIP-mediated release with the effects of PACAP-38 and 8-bromo cAMP.
Main Results:
- VIP induced the release of TNF-alpha, IL-3, G-CSF, and M-CSF from astrocytes, a novel finding.
- Cytokine release was rapid (15-30 min) and involved both depletion of cytosolic stores and potentially de novo synthesis.
- VIP demonstrated higher efficacy than PACAP-38 in cytokine release, with distinct potency differences for specific cytokines, suggesting a non-cAMP-dependent pathway for VIP.
Conclusions:
- VIP triggers a complex array of cytokine release from astrocytes via multiple mechanisms.
- A cAMP-mediated pathway, likely involving VPAC receptors, contributes to low-efficacy release induced by PACAP-38.
- A distinct, high-efficacy, VIP-preferring mechanism, not linked to cAMP, also mediates cytokine release, potentially contributing to VIP's neurotrophic roles.