NGF and Its Receptors in the Regulation of Inflammatory Response

Abstract

There is growing interest in the complex relationship between the nervous and immune systems and how its alteration can affect homeostasis and result in the development of inflammatory diseases. A key mediator in cross-talk between the two systems is nerve growth factor (NGF), which can influence both neuronal cell function and immune cell activity. The up-regulation of NGF described in inflamed tissues of many diseases can regulate innervation and neuronal activity of peripheral neurons, inducing the release of immune-active neuropeptides and neurotransmitters, but can also directly influence innate and adaptive immune responses. Expression of the NGF receptors tropomyosin receptor kinase A (TrkA) and p75 neurotrophin receptor (p75NTR) is dynamically regulated in immune cells, suggesting a varying requirement for NGF depending on their state of differentiation and functional activity. NGF has a variety of effects that can be either pro-inflammatory or anti-inflammatory. This apparent contradiction can be explained by considering NGF as part of an endogenous mechanism that, while activating immune responses, also activates pathways necessary to dampen the inflammatory response and limit tissue damage. Decreases in TrkA expression, such as that recently demonstrated in immune cells of arthritis patients, might prevent the activation by NGF of regulatory feed-back mechanisms, thus contributing to the development and maintenance of chronic inflammation.

p75NTR regulates brain mononuclear cell function and neuronal structure in Toxoplasma infection‐induced neuroinflammation

“…However, the molecular and cellular mechanisms mediating such interaction remained unexplored (Parlog et al, 2015). Neurotrophin signaling has been shown to modulate the immune system activity at different levels (Minnone, de Benedetti, & Bracci-Laudiero, 2017;Vega et al, 2003). Therefore, we investigated the role of p75 NTR signaling in modulating neuronal architecture and immune cell function in the CNS.…”

The role and relevance of mast cells in urticaria

“…This would increase the sensitivity of the skin in the local environment to neurogenic flare, itch, and pain. NGF also promotes local inflammatory responses as it promotes the proliferation, survival, and activation many immune cells, including mast cells, Th2‐lymphocytes, neutrophils, and eosinophils . Of particular relevance to urticaria is the ability of NGF to increase the local accumulation of mast cells .…”

“…[165][166][167][168] The primary effect of NGF is on the local development of sensory nerves which become NGF-dependent near the target tissue. 169 Thus, at sites of local inflammation, the axons grow toward a higher concentration of NGF,…”

“…NGF also promotes local inflammatory responses as it promotes the proliferation, survival, and activation many immune cells, including mast cells, Th2-lymphocytes, neutrophils, and eosinophils. 169 Of particular relevance to urticaria is the ability of NGF to increase the local accumulation of mast cells. 171,172 However, in contrast to the neuropeptides substance P and VIP, NGF does not stimulate mast cell degranulation.…”

Dissatisfaction with management of musculoskeletal pain: A global problem and methods of its solution

“…[4,5]. Так, один из наиболее изу-ченных нейромедиаторов -фактор роста нервов (ФРН) -оказывает существенное влияние на развитие иммунного воспаления, стимулируя пролиферацию и дифференциров-ку CD4 T-лимфоцитов (Т-хелперов) [6]. Провоспалитель-ным потенциалом обладают такие нейромедиаторы, актив-но синтезируемые нейроглией и самими нервными оконча-ниями, как кальцитонин-родственный пептид, тахикинины (в частности, субстанция Р), меланокортины, вазоактивный интестинальный пептид, гипофизарный полипептид, акти-вирующий аденилатциклазу (PACAP), грелин и др.…”