Effects of Nerve Growth Factor on the Expression of Interleukin‐2 Receptors on Cultured Human Lymphocytes

Jiang

The American Journal of Pathology

2008

Nerve growth factor (NGF) influences the key pathological events of psoriasis: keratinocyte proliferation, angiogenesis, and T-cell activation. We have systematically examined the kinetics of NGF expression, keratinocyte proliferation, and migration of T lymphocytes in the epidermis in Koebner-induced developing psoriatic plaques. In skin traumatized by the tape-stripping method (n ‫؍‬ 12), a marked up-regulation of NGF in Koebner-positive lesions (n ‫؍‬ 7) was observed 24 hours after trauma. Synthesis of NGF reached its maximum level in the 2nd week. Furthermore, cultured keratinocytes from nonlesional skin of psoriasis patients produced 10 times higher levels of NGF compared with keratinocytes from healthy individuals. To substantiate the in vivo effect of NGF secreted by keratinocytes in psoriatic plaques, we studied psoriatic plaques and normal human skin in a SCID-human skin xenograft model. The transplanted psoriatic plaques demonstrated marked proliferation of NGF-R (p75)-positive nerve fibers compared with only a few nerves in the transplanted normal human skin. Our results demonstrate that 1) in a developing psoriatic lesion, up-regulation of NGF together with keratinocyte proliferation are early events and precede epidermotropism of T lymphocytes; 2) keratinocytes in patients with psoriasis are primed to produce elevated levels of NGF; and 3) NGF synthesized by these keratinocytes is functionally active.

Section: Discussionmentioning

confidence: 99%

Revisiting the Koebner Phenomenon

Jiang

The American Journal of Pathology

2008

“…Studies on mature lymphoid cells demonstrated that NGF has a dose-dependent prohferative effect on both B and T cells (90,91) and causes differentiation of B cells into immunoglobulin-secreting plasma cells (91). NGF stimulates B cells to produce IgM, IgA, and IgG (91)(92)(93)(94) and can also induce high-affinity IL-2 receptors on human peripheral blood mononuclear cells (93,95).…”

Section: Ngf and The Immune Systemmentioning

confidence: 99%

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

Aloe

Bracci-Laudiero

Бонини

et al. 1997

Allergy

203

127

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.

European Journal of Biochemistry

“…Recently, NGF-mediated proliferation of mast cells in the rat joint synovium has also been reported [23]. In addition NGF has been demonstrated to modulate the proliferation [24-261 and differentiation [25,271 of B lymphocytes and the expression of interleukin-2 receptors in B lymphocytes [28] and T lymphocytes [29]. Moreover, NGF synthesis in non-neuronal cells is modulated by inflammatory stimuli [30] and cytokines .…”

mentioning

confidence: 99%

Expression of mRNA encoding neurotrophins and neurotrophin receptors in rat thymus, spleen tissue and immunocompetent cells

Laurenzi

Barbany

Timmusk

et al. 1994

The expression of neurotrophin and neurotrophin receptor mRNAs was examined using RNase protection assays and Northern‐blot analysis in rat thymus, spleen tissue and immunocompetent mononuclear cells purified from these two organs. Nerve growth factor, brain‐derived neurotrophic factor, neurotrophin‐3 and neurotrophin‐4 mRNAs were all expressed in thymus and spleen tissue although at different levels, while immunocompetent cells expressed neurotrophin‐3 and neurotrophin‐4 mRNAs. Thymus and spleen tissue expressed mRNAs encoding the low‐affinity nervegrowth‐factor receptor, the non‐neuronal TrkA I receptor, the truncated (kinase deficient) and full‐length TrkB, and the TrkC receptor. Low‐affinity nerve‐growth‐factor receptor and non‐neuronal TrkA I mRNAs were detected in both thymus and spleen immunocompetent cells. In addition, thymus cells expressed neuronal TrkA II mRNA and spleen cells expressed truncated TrkB mRNA. The expression of TrkA I and TrkA II mRNAs was enhanced in both thymus and spleen cells after cell culture. Enhanced levels of neurotrophin‐4 mRNA were observed in spleen immunocompetent cells after adrenalectomy. Moreover, the expression of neurotrophin‐4 mRNA was up‐regulated after stimulation of immune cells with the mitogens concanavalin A or lipopolysaccharide or with the inflammatory mediator leukotriene B4. This suggests that neurotrophin‐4 could be secreted by immunocompetent cells and may be involved in inflammatory processes.