High affinity interkakin-6 binding sites in bovine hypothalamus

Cornfield, Linda J.; Sills, Matthew A.

doi:10.1016/0014-2999(91)90263-p

Cited by 38 publications

(17 citation statements)

References 6 publications

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“…In addition, in in situ hybridization studies, IL-6 was predominantly expressed by hypothalamic neurons [10]. All these observations suggest that neurons may also be a source of cytokine synthesis and release, as well as the site of action of these substances.…”

Section: Introductionmentioning

confidence: 81%

Hypothalamic Relationships between Interleukin-6 and LHRH Release Affected by Bacterial Endotoxin in Adult Male Rats

Feleder

Wuttke²,

Moguilevsky³

1998

Neurosignals

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Immune system alterations coexist with modifications in the reproductive axis. The bacterial endotoxin lipopolysaccharide (LPS) has inflammatory effects and stimulates cytokine release in the hypothalamus where LHRH neurons are located. LPS inhibition of LHRH release at hypothalamic level appears to be associated with modifications in the cerebral immune system. Central and peripheral LPS administration induces the expression and release of several cytokines in the central nervous system. Hence the present study was designed to investigate a possible function of the interleukin-6 (IL-6) stimulated by LPS in the regulation of LHRH secretion. Male rats were decapitated, and the preoptic mediobasal hypothalamic area (PO/MBH) was dissected and superfused with Earle’s balanced salt solution. Superfusate fractions were collected at 15-min intervals after a 60-min stabilization superfusion period. LPS (100 ng/ml) and IL-6 receptor antagonist (IL-6ra) were then added to the superfusion medium over 1 h in two different experimental designs: (1) LPS only and (2) LPS followed by IL-6ra, performed in different experiments. This was followed by a washout period. The PO/MBH fragments were then subjected to a 56 mM K⁺ stimulus. Control PO/MBH fragments were continuously superfused with Earle’s solution. As expected, LHRH release was significantly reduced (p < 0.05) during and following exposure to LPS. At the same time, IL-6 concentrations significantly increased in the superfusion medium compared with the control group. IL-6ra significantly (p < 0.01) potentiated the inhibitory effect of LPS on LHRH secretion. On the bases of previous papers indicating a stimulatory effect of IL-6 on LHRH release it could be considered that the potentiation of IL-6ra of the inhibitory effect of LPS on LHRH could be the consequence of the lack of the stimulatory effect of IL-6 on LHRH produced by the receptor antagonist. IL-6ra also increased IL-6 levels measured in medium probably due to a decrease in the metabolization induced by the blockage of the receptors and the consequent accumulation of IL-6 in the media. These results could indicate that IL-6 partly attenuates the inhibitory effect of LPS on LHRH release. These observations indicate that there is an increase in IL-6 release that becomes significant at the same time when LHRH release is decreased. Also, depolarizing concentrations of K⁺ (56 mM) did not increase IL-6 release, while LHRH release from the hypothalamic fragments was significantly increased. These data suggest that the inhibitory effect of LPS on LHRH release may be explained by the stimulation of other cytokines than IL-6, meanwhile the augmented levels of IL-6 probably released via a nonneuronal source was shown to be higher when LHRH was decresed. This could confirm the stimulatory role of IL-6 on LHRH release.

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Section: Introductionmentioning

confidence: 81%

Hypothalamic Relationships between Interleukin-6 and LHRH Release Affected by Bacterial Endotoxin in Adult Male Rats

Feleder

Wuttke²,

Moguilevsky³

1998

Neurosignals

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“…Until recently, the location and nature of this ILGR in the brain was not known. Using bovine hypothalamic membranes, Cornfield and Sills (1991) (gp130) alone has no IL6 binding activity but with the (Y chain gives rise to a high affinity receptor: gp130 is the signal-transducing chain of the receptor complex; gp130 itself contains a large intracytoplasmic domain lacking homology with protein kinases and without known catalytic activities. Stimulation of target cells with a complex of soluble IL6R and IL6 induces homodimerization and tyrosine-specific phosphorylation of gp130 (Kishimot0 et al, 1992a,b).…”

Section: Ilg/cntf/lif Receptor Familymentioning

confidence: 99%

Cytokine receptors on glial cells

Otero

Merrill

1994

Glia

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Given what evidence there is for the molecular and functional nature of cytokines and their cognate binding proteins in the immune system and the emerging similarities or even identities for these ligands and receptors in the nervous system, two general models may be relevant. The first emerging pattern is that receptors for related but distinct trophic factors in the CNS are in many instances multichain complexes with one or more shared components. The shared components of the receptor complex may be either signal- or nonsignal-transducing chains. A second emerging motif is that related ligands and related receptors fall into gene families. Undoubtedly, these models will facilitate the cloning of novel members of these families whose function is quite specific to the nervous system and in particular to glial cells. This article will review the function of the receptors for cytokines and families of differentiation/survival/growth factors as they operate on astrocytes, microglia, and oligodendrocytes in development, health, and disease.

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“…Further studies have revealed that IL-6 is selectively expressed in brain structures. Cornfield and Sills (1991) have reported the existence of high affinity IL-6 binding sites in the hypothalamus. High levels of IL-6 mRNA expression have been detected in the hippocampus, neocortex and cerebellum (Gadient and Otten, 1994).…”

Section: Introductionmentioning

confidence: 97%