Regulation of β‐nerve growth factor expression by inflammatory mediators in hippocampal cultures

Friedman, Wilma J.; Lärkfors, Lena; Ayer-LeLièvre, Christiane; Ebendal, Ted; Olson, Lar̀s; Persson, Håkan

doi:10.1002/jnr.490270316

Cited by 93 publications

(58 citation statements)

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“…Indomethacin acts by inhibiting cyclo-oxygenase and subsequently prostaglandin E2 (PGE2) synthesis (Rome & Lands, 1975). PGE2 has been found to elicit a dose-dependent increase in both NGF protein and mRNA levels in rat hippocampal cell cultures (Friedman et al, 1990), but an involvement of eicosanoids in NGF production in peripheral tissues has not been reported. The lower dose of indomethacin would be expected to have substantially and irreversibly inhibited cyclo-oxygenase (Salmon et al, 1983) but it had minimal actions on behavioural sensitivity or IL-iP/NGF levels, implying that the effects seen with the higher dose may be due to some other action of indomethacin.…”

Section: Discussionmentioning

confidence: 99%

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Safieh‐Garabedian

Poole

Allchorne

et al. 1995

British J Pharmacology

552

324

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Peripheral inflammation is associated with the local production of neuroactive inflammatory cytokines and growth factors. These may contribute to inflammatory pain and hyperalgesia by directly or indirectly altering the function or chemical phenotype of responsive primary sensory neurones. To investigate this, inflammation was produced by the intraplantar injection of complete Freund's adjuvant (CFA) in adult rats. This resulted in a significant elevation in interleukin‐ip (IL‐1β) and nerve growth factor (NGF) levels in the inflamed tissue and of the peptides, substance P and calcitonin gene‐related peptide (CGRP) in the L4 dorsal root ganglion 48 h post CFA injection. The effects of a steroidal (dexamethasone) and a non‐steroidal (indomethacin) anti‐inflammatory drug on the levels of NGF and IL‐1β in inflamed tissue were investigated and compared with alterations in behavioural hyperalgesia and neuropeptide expression in sensory neurones. Systemic dexamethasone (120 μg kg−1 per day starting the day before the CFA injection) had no effect on the inflammatory hyperalgesia. When the dose was administered 3 times daily, a reduction in mechanical and to a lesser extent thermal sensitivity occurred. Indomethacin at 2 mg kg−1 daily (i.p.) had no effect on the hyperalgesia and a dose of 4 mg kg−1 daily was required to reduce significantly mechanical and thermal hypersensitivity. The increase in NGF produced by the CFA inflammation was prevented by both dexamethasone and indomethacin, but only at the higher dose levels. Dexamethasone at the lower and higher dose regimes diminished the upregulation of IL‐1β whereas indomethacin had an effect only at the higher dose. The increase in SP and CGRP levels produced by the CFA inflammation was prevented by dexamethasone and indomethacin at the lower and higher dose regimes. Intraplantar injections of IL‐1β (0.01, 0.1 and 1 ng) produced a brief (6 h) thermal hyperalgesia and an elevation in cutaneous NGF levels which was prevented by pretreatment with human recombinant IL‐1 receptor antagonist (IL‐1 ra) (0.625 μg, i.v.). The thermal hyperalgesia but not the NGF elevation produced by intraplantar IL‐1β (1 ng) was prevented by administration of a polyclonal neutralizing anti‐NGF serum. IL‐1 ra significantly reduced the mechanical hyperalgesia produced by CFA for 6 h after administration as well as the CFA‐induced elevation in NGF levels. Anti‐NGF pretreatment substantially reduced CFA‐induced mechanical and thermal hyperalgesia without reducing the elevation in IL‐1β. Intraplantar NGF (0.O2, 0.2 and 2 μg) injections produced a short lasting thermal and mechanical hyperalgesia but did not change IL‐1β levels in the hindpaw skin. Our results demonstrate that IL‐1β contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Safieh‐Garabedian

Poole

Allchorne

et al. 1995

British J Pharmacology

552

324

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“…As tiientioned above, in addition to the allergic disease VKC, other forms of allergic diseases are also characterized by a significant augmentation of blood NGF levels (27). It was shown that patients affected by asthma and/or rhinocotijunctivitis, and/ or urticaria/angioedema were clinically characterized by bronchial reactivity, total and specific IgE, circulating eosinophil cationic protein serum levels, and a high level of circulating NGF.…”

Section: Ngf and Allergymentioning

confidence: 95%

“…Thus, NGF is involved in the mechanisms related to regulation of immune cell prohferation, differentiation, and activation. The observations that cytokines affect NGF synthesis (27,28,30), differences in tissue cytokines, and NGF expression, either alone or in combination, may be functionally correlated in these disorders. However, in at least one case, anti-NGF antibodies were shown to prevent the wasting induced by TNF-a in transgenic arthritic mice overexpressing this cytokine (102).…”

Section: Ngf and The Immune Systemmentioning

confidence: 99%

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The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

Aloe

Bracci-Laudiero

Бонини

et al. 1997

Allergy

204

127

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Numerous studies published in the last 10–15 years have shown that nerve growth factor (NGF), a polypeptide originally discovered in connection with its neurotrophic activity, also acts on cells of the immune system. NGF has been found in various immune organs including the spleen, lymph nodes, and thymus, and cells such as mast cells, eosinophils, and B and T cells. The circulating levels of NGF increase in inflammatory responses, in various autoimmune diseases, in parasitic infections, and in allergic diseases. Stress‐related events both in animal models and in man also result in an increase of NGF, suggesting that this molecule is involved in neuroendocrine functions. The rapid release of NGF is part of an alerting signal in response to either psychologically stressful or anxiogenic conditions in response to homeostatic alteration. Thus, the inflammation and stress‐induced increase in NGF might alone or in association with other biologic mediators induce the activation of immune cells during immunologic insults. A clearer understanding of the role of NGF in these events may be useful to identify the mechanisms implicated in certain neuroimmune and immune dysfunctions.

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“…Higher plasma levels of these NTs have also been described in type 1 diabetic patients (22). Other studies indicate elevated NGF production and release associated with an increase in several proinflammatory cytokines, such as TNFa and IL-1b (23,24). We have demonstrated a marked stimulation of NGF expression and secretion in murine and human adipocytes by TNFa, prostaglandin PGD 2 and J 2 series prostaglandins PGJ 2 , and D 12 -PGJ 2 (25), emphasizing the link between this NT and inflammatory processes.…”

Section: Introductionmentioning

confidence: 94%

Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women

et al. 2007

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Objective: Neurotrophins (NTs) could be involved in the development and progression of inflammatory and immune diseases. Because obesity and the metabolic syndrome (MetSyn) are related to a lowgrade systemic inflammation, plasma NT levels (neurotrophinemia) could play an important role in the ethiopathogenic mechanisms underlying these metabolic derangements. This is the first study evaluating the plasma NT levels in a group of women with obesity and MetSyn, and also the adipose tissue nerve growth factor (NGF) expression in a small group of them. Methods: Included were 146 adult women with different degrees of adiposity, with or without MetSyn. Plasma NT levels were measured. NGF expression was analyzed in s.c. adipose tissue of a subgroup of morbidly obese and normal-weight females. Results: NGF plasma levels were 1.4-fold higher in overweight and obese subjects. Plasma NGF was, however, lower in a group of morbidly obese subjects than in overweight or obesity, but it remained elevated relative to the normal-weight group. Plasma NGF was significantly correlated with body mass index (BMI), percentage body fat, and waist circumference in non-morbidly obese subjects. NGF was positively related to inflammatory markers. NT3 and brain-derived neurotrophin factor seem to be more related to lipid profile than to BMI, adipose tissue distribution, or peripheral inflammatory markers. Subjects with type 2 diabetes, abdominal fat distribution, or the MetSyn showed significantly higher levels of NGF. The MetSyn was the only independent predictor of the variability observed in the NGF plasma values. Conclusion: NGF is upregulated in obesity, type 2 diabetes, and the MetSyn. Whether this NT may contribute to inflammation and the metabolic derangements associated with body weight gain remains to be elucidated.

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Regulation of β‐nerve growth factor expression by inflammatory mediators in hippocampal cultures

Cited by 93 publications

References 50 publications

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases

Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women

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