Inhibition of IGF-I–related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes

Choukair, Daniela; Hügel, Ulrike; Sander, Anja; Uhlmann, Lorenz; Tönshoff, Burkhard

doi:10.1038/pr.2014.84

Cited by 30 publications

(26 citation statements)

References 33 publications

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“…The inflammatory state exerts an inhibition on GH and IGF-1 bioactivity [ 168 ]. Pro-inflammatory cytokines reduce JAK2 and STAT activation through the stimulation of suppressor of cytokine signaling (SOCS) proteins, which are a central component of the regulation of GH and IGF-1 action [ 169 ] and inhibition of IGF-1 signaling pathway [ 170 ]. Pro-inflammatory cytokines inhibit the nuclear factor-κB (NF-κB), which play an important role in the regulation of GH/IGF-1 signaling [ 171 ], so that, during the neurodegenerative process, the effect of GH and IGF-1 therapy could be canceled by high cytokine expression at the cellular level.…”

Section: Discussionmentioning

confidence: 99%

Neurotrophic and Neuroregenerative Effects of GH/IGF1

Bianchi¹,

Locatelli

Rizzi

2017

IJMS

161

109

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Introduction. Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects. Methods. In the literature, we searched the clinical trials and followed up studies in humans, which have evaluated the effect of GH/IGF-1 on CNS and PNS. The following keywords have been used: “GH/IGF-1” associated with “neuroregeneration”, “amyotrophic lateral sclerosis”, “Alzheimer disease”, “Parkinson’s disease”, “brain”, and “neuron”. Results. Of the retrieved articles, we found nine articles about the effect of GH in healthy patients who suffered from traumatic brain injury (TBI), and six studies (four using IGF-1 and two GH therapy) in patients with amyotrophic lateral sclerosis (ALS). The administration of GH in patients after TBI showed a significantly positive recovery of brain and mental function. Treatment with GH and IGF-1 therapy in ALS produced contradictory results. Conclusions. Although strong findings have shown the positive effects of GH/IGF-1 administration on neuroregeneration in animal models, a very limited number of clinical studies have been conducted in humans. GH/IGF-1 therapy had different effects in patients with TBI, evidencing a high recovery of neurons and clinical outcome, while in ALS patients, the results are contradictory. More complex clinical protocols are necessary to evaluate the effect of GH/IGF-1 efficacy in neurodegenerative diseases. It seems evident that GH and IGF-1 therapy favors the optimal recovery of neurons when a consistent residual activity is still present. Furthermore, the effect of GH/IGF-1 could be mediated by, or be overlapped with that of other hormones, such as estradiol and testosterone.

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Section: Discussionmentioning

confidence: 99%

Neurotrophic and Neuroregenerative Effects of GH/IGF1

Bianchi¹,

Locatelli

Rizzi

2017

IJMS

161

109

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“…This is based on the principle that GH regulates the expression of locally produced IGF-I, which then acts in an autocrine/paracrine manner. Pro-inflammatory cytokines, such as TNF-alpha, interfere both with circulating IGF-I production resulting in hepatic GH resistance ( 22 ) and with the action of locally produced IGF-I by decreasing proliferation and differentiation of chondrocytes in the growth plate ( 23 ).…”

Section: Physiology Of Gh–igf-i Axismentioning

confidence: 99%

The growth hormone–insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders

Blum

Al‐Herbish²,

Alsagheir

et al. 2018

Endocrine Connections

114

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The growth hormone (GH)–insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGF-binding protein (IGFBP)-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.

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“…The IGF-1 signalling pathway may also be altered in chronic inflammatory conditions. Several authors showed how TNF-α, IL-6, and IL-1β dysregulate IGF-1 intracellular mediators MAPK/extracellular signal-regulated kinases (ERKs), and phosphoinositide 3-kinase (PI3K), in chondrocytes [ 73 , 74 , 75 ]. Inflammation is sustained by the activation of several immune cell types which secrete soluble cytokines, as chemokines, interferons, and ILs, activating bone resorption and inhibiting bone growth/formation processes at local and systemic levels [ 76 ].…”

Section: Interactions Between Pro-inflammatory Cytokines and Gh–igmentioning

confidence: 99%

Inflammatory Diseases and Growth: Effects on the GH–IGF Axis and on Growth Plate

Cirillo

Lazzeroni

Sartori

et al. 2017

IJMS

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This review briefly describes the most common chronic inflammatory diseases in childhood, such as cystic fibrosis (CF), inflammatory bowel diseases (IBDs), juvenile idiopathic arthritis (JIA), and intrauterine growth restriction (IUGR) that can be considered, as such, for the changes reported in the placenta and cord blood of these subjects. Changes in growth hormone (GH) secretion, GH resistance, and changes in the insulin-like growth factor (IGF) system are described mainly in relationship with the increase in nuclear factor-κB (NF-κB) and pro-inflammatory cytokines. Changes in the growth plate are also reported as well as a potential role for microRNAs (miRNAs) and thus epigenetic changes in chronic inflammation. Many mechanisms leading to growth failure are currently known; however, it is clear that further research in the field is still warranted.

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Inhibition of IGF-I–related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes

Cited by 30 publications

References 33 publications

Neurotrophic and Neuroregenerative Effects of GH/IGF1

Neurotrophic and Neuroregenerative Effects of GH/IGF1

The growth hormone–insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders

Inflammatory Diseases and Growth: Effects on the GH–IGF Axis and on Growth Plate

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