INTERFERON-α AND TRANSFORMING GROWTH FACTOR-β1 REGULATE CORTICOTROPIN-RELEASING FACTOR RELEASE FROM THE AMYGDALA: COMPARISON WITH THE HYPOTHALAMIC RESPONSE

doi:10.1016/S0197-0186(96)00082-4

Neurochemistry International

Volume 30, Issues 4–5, April–May 1997, Pages 455-463

https://doi.org/10.1016/S0197-0186(96)00082-4 Get rights and content

Abstract

Interferon-α (IFN-α) and transforming growth factor-β₁ (TGF-β₁) have been reported in different brain regions. The amygdala contains high levels of corticotropin releasing factor (CRF) and has been implicated as a central site for its stress-related autonomic and behavioral response. IFN-α will release arginine vasopressin (AVP) from both amygdala and hypothalamus, which further supports a role for the amygdala in neuroimmune interactions. In the present study, we compared the effects of these cytokines on the in vitro release of CRF from the amygdala and hypothalamus. In addition, we evaluated the possible involvement of guanylate cyclase-mediated signaling in CRF release. IFN-α stimulates CRF release from both amygdala and hypothalamus. The CRF release by IFN-α, Interleukin-2 (IL-2) and acetylcholine is blocked by guanylate cyclase inhibitors, indicating a role for cGMP accumulation in this CRF release. TGF-β₁ had no effect on basal release of CRF, nor on the CRF-release induced by IL-2, but selectively blocked the acetylcholine-induced release in both amygdala and hypothalamus. Taken with a previous report that TGF-β₁ specifically inhibits AVP release by acetylcholine, these results suggest that TGF-β₁ may modulate HPA axis activation, by antagonizing (acetylcholine-evoked) CRF and AVP release. These data further support a role for the amygdala in the bidirectional communication between neuroendocrine and immune system. © 1997 Elsevier Science Ltd. All rights reserved

Section snippets

Materials

Human recombinant IL-2 and aprotinin were from Boehringer Mannheim (Indianapolis, IN). Murine recombinant IFN-α and Earle's salt solution was supplied by Gibco BRL (Gaithersburg, MD). Acetylcholine, bacitracin, PMSF, methylene blue trihydrate and glucose were from Sigma (St Louis, MO). LY-83583 was from Calbiochem Biochemicals (San Diego, CA). Bovine albumin was supplied by Pentex (Kankakee, IL). Ascorbic acid was from Fischer (Pittsburgh, PA). Costar supplied 48-multiwell plates. A specific

Effect of IFN-α on the basal CRF release from the amygdala and hypothalamus

As shown in Fig. 1(A) and (B), a 20 min IFN-α incubation stimulated CRF release from both the amygdala as well as the hypothalamus to a similar extent. IFN-α at 1 U/ml did not significantly increase CRF release from the amygdala and hypothalamus compared to basal levels. There was a significant increase observed after 20 min exposure to IFN-α at 50, 100, or 250 U/ml, which was transient and did not persist after the second IFN-α incubation period.

Effect of TGF-β₁ on the acetylcholine- and IL-2-induced CRF release.

To study whether TGF-β₁ can modulate

DISCUSSION

Our results provide evidence for a rapid release of CRF by IFN-α, not only from the rat amygdala, but also from the hypothalamus in vitro. In addition, our findings demonstrate that TGF-β₁ selectively blocks the acetylcholine-induced CRF release from both brain regions, while having no effect on basal release nor on the CRF-release triggered by IL-2. Finally, guanylate cyclase inhibitors block CRF release induced by IFN-α, IL-2 and acetylcholine.

TGF-β₁ INHIBITION OF ACETYLCHOLINE-EVOKED CRF RELEASE

The inhibition of the acetylcholine-evoked CRF release from both the amygdala and hypothalamus by TGF-β₁ (Fig. 2), in addition to that reported for acetylcholine-evoked AVP release from both brain regions (Raber and Bloom, 1996), provides further support for its modulation of the cholinergic response. Acetylcholine seems to be important for neuroimmune interactions. Lymphocytes respond to and are able to produce and degrade acetylcholine, and changes in cholinergic tonus affect immune signaling

CONCLUSION

CRF mediates stress-induced immunomodulatory functions (Irwin et al., 1993). During stress, IFNs can be produced in large quantities and is often associated with neurotoxicity (Merimsky et al., 1990; Gutterman, 1994). The modulation of CRF release by IFN-α could contribute to the toxic effects of high brain levels of IFN-α. Stimulated lymphocytes can produce a variety of neuropeptides through activation of the propiomelanocortin gene concurrently with IFN production. The neurotoxic effects of

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^*: This work was supported by the NIMH AIDS Center, Grant MH 47680, and the Schumacher-Kramer Foundation.

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INTERFERON-α AND TRANSFORMING GROWTH FACTOR-β1 REGULATE CORTICOTROPIN-RELEASING FACTOR RELEASE FROM THE AMYGDALA: COMPARISON WITH THE HYPOTHALAMIC RESPONSE*

Abstract

Section snippets

Materials

Effect of IFN-α on the basal CRF release from the amygdala and hypothalamus

Effect of TGF-β1 on the acetylcholine- and IL-2-induced CRF release.

DISCUSSION

TGF-β1 INHIBITION OF ACETYLCHOLINE-EVOKED CRF RELEASE

CONCLUSION

J. Neuroimmunol.

J. Neuroimmunol.

Peptides

Neurosci. Lett.

J. Steroid Biochem. mol. Biol.

Regul. Peptides

Life Sci.

Sem. Neurosci.

Peptides

Brain Res.

J. Neuroimmunol.

Brain Res.

Neurosci. Lett.

Brain Res.

Int. J. Immunopharmacol.

Biochem. Pharmacol.

Eur. J. Cancer

Neuroscience

Immunol. Lett.

J. Neuroimmunol.

Brain Res.

Biochem. biophys. Res. Comm.

Brain Res.

Life Sci.

Neuroscience

Impaired recognition of emotion in facial expression following bilateral damage to the human amygdala

Nature

Hypothalamic control of adrenocorticotrophin secretion: advances since the discovery of 41-residue corticotropin-releasing factor

Endocr. Rev.

Distribution of corticotrophin-releasing factor like immunoreactivity in squirrel monkey (Saimiri sciureus) amygdala

J. comp. Neurol.

The immune-hypothalamic-pituitary-adrenal axis

Endocr. Rev.

Influence of the central nucleus of the amygdala on the content of corticotropin-releasing factor in the median eminence

Neuroendocrinology

Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum

Proc. natn. Acad. Sci. USA.

Accumulation of 3H-phosphoinositides mediated by muscarinic receptors in the developing chick retina: inhibition of carbachol-induced response by glutamate receptors

J. Neurochem.

Morphology of peptide-immunereactive neurons in the rat central nucleus of the amygdala

J. Comp. Neurol.

Alterations in corticotrophin-releasing factor-like immunoreactivity in discrete rat brain regions after acute and chronic stress

J. Neurosci.

The concepts of stress and stress system disorders: overview of physical and behavioural homeostasis

J. Am. Med. Assoc.

Corticotrophin-releasing factor immunoreactivity is widely distributed within the central nervous system of the rat: an immunohistochemical study

J. Neurosci.

Transforming growth factor-β 1 (TGF-β1) expression and regulation in rat cortical astrocytes

J. Neuroimmunol.

Plasma corticosterone responses to electrical stimulation of the amygdaloid comples: cytoarchitectural specificity

Neuroendocrinol.

The effect of CRF antagonist on immobilization stress-induced increases in noradrenaline release in rat brain regions

Yakabutsu Seishin Kodo

Neurotoxic and other side effects of high-dose interferon in amyotrophic lateral sclerosis

Acta Neurol. Scand.

Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in brain

Nature

Interferon-α stimulates the hypothalamo-pituitary-adrenal axis in vivo and in vitro

Neuroendocrinol.

INTERFERON-α AND TRANSFORMING GROWTH FACTOR-β₁ REGULATE CORTICOTROPIN-RELEASING FACTOR RELEASE FROM THE AMYGDALA: COMPARISON WITH THE HYPOTHALAMIC RESPONSE*

Effect of TGF-β₁ on the acetylcholine- and IL-2-induced CRF release.

TGF-β₁ INHIBITION OF ACETYLCHOLINE-EVOKED CRF RELEASE

Accumulation of ³H-phosphoinositides mediated by muscarinic receptors in the developing chick retina: inhibition of carbachol-induced response by glutamate receptors

Transforming growth factor-β 1 (TGF-β₁) expression and regulation in rat cortical astrocytes