Effects of Anti-Nerve Growth Factor Antibody on Symptoms in the NC/Nga Mouse, an Atopic Dermatitis Model

Takano, Norikazu; Sakurai, Takanobu; Kurachi, Michio

doi:10.1254/jphs.fp0050564

Cited by 81 publications

(69 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Intraperitoneal administration of anti-nGf neutralizing antibody to atopic nc/nga mice significantly attenuated both the increased number of nerve fibers in the epidermis and scratching behavior, but did not ameliorate scratching that had already developed. 52) Similarly, application of the TrkA antagonists AG879 and K252a to the nape of atopic nc/nga mice significantly improved established dermatitis and scratching behavior and reduced the numbers of nerve fibers in the epidermis, suggesting the importance of nGf in the pathogenesis of atopic dermatitis-like skin lesions. 53) thus, nGf and its receptors may be among the antipruritic targets in pruritic skin diseases such as atopic dermatitis.…”

Section: Anti-ngf Antibody and Ngf Receptor Antagonistsmentioning

confidence: 93%

An Update on Peripheral Mechanisms and Treatments of Itch

Tominaga

Takamori

2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Histamine H 1 -receptor blockers are used to treat all types of itch resulting from serious skin diseases such as atopic dermatitis, as well as from renal and liver diseases. However, they often lack efficacy in chronic itch, a profound clinical problem that decreases quality of life. The development of effective treatments requires a full understanding of the fundamental mechanisms of itch. Recent studies have indicated that the pathogenic mechanisms of itch also involve agonists other than histamine, including proteases, neuropeptides, cytokines, and opioids, as well as their cognate receptors. Release of these pruritogenic mediators and modulators into the periphery may directly activate itch-mediating C-fibers via specific receptors on the nerve terminals. Histological observations have shown increased epidermal nerve densities in patients with atopic dermatitis, suggesting that the higher density is at least partly responsible for itch sensitization. This

show abstract

Section: Anti-ngf Antibody and Ngf Receptor Antagonistsmentioning

confidence: 93%

An Update on Peripheral Mechanisms and Treatments of Itch

Tominaga

Takamori

2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…In this study, tacrolimus and RG (1%) inhibited DNFB-induced NGF mRNA expression. In consideration of the previous report (35), NGF seems to be an important regulator of nerve fiber extension.…”

Section: Discussionmentioning

confidence: 71%

“…It has also been reported that NGF is abundantly released from human keratinocytes in vitro (34) and highly expressed in the epidermis of NC/Nga mice (35,36). Furthermore, in NC/Nga mice, treatment with an anti-NGF antibody abolished nerve fiber extension as well as skin lesions (35).…”

Section: Discussionmentioning

confidence: 94%

Red Ginseng Inhibits Scratching Behavior Associated With Atopic Dermatitis in Experimental Animal Models

Samukawa¹,

Izumi²,

Shiota³

et al. 2012

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. Pruritus is a severe symptom that is difficult to treat in atopic dermatitis patients. Red ginseng (RG), a natural medicine, has various biological activities such as anti-inflammatory effects. In this study, we examined the efficacy of RG extract (RGE) and its mechanism on experimental atopic dermatitis in mice. The effects of RGE on vascular permeability and itching were first evaluated. Histamine-induced permeability and itching were significantly inhibited by embrocation with RGE as well as diphenhydramine, an antihistamine drug. Next, we assessed the therapeutic effect of topical RGE in a mouse model of atopic dermatitis. Dermatitis was induced by repeated application of 2,4-dinitrofluorobenzene (DNFB) acetone solution to the mouse ear. The effects of tacrolimus (a calcineurin blocker), dexamethasone (a corticosteroid), and RGE on dermatitis and associated scratching behavior were compared. Repeated DNFB application caused frequent scratching behaviors and ear swelling. Topical treatment with tacrolimus, dexamethasone, and RGE for 8 days before the final challenge with DNFB significantly inhibited ear swelling. Tacrolimus and RGE significantly inhibited scratching behavior, whereas dexamethasone failed to do so. DNFB-induced nerve growth factor expression and nerve fiber extension were significantly attenuated by tacrolimus and RGE, but not by dexamethasone. RGE may have the potential for treatment of atopic dermatitis.

show abstract

“…In fact, high-affinity NGF-receptor inhibitors, AG879 and K252a, are effective in improving the established dermatitis (50) and scratching behavior in the NC/Nga atopic dermatitis model mouse (51), and anti-NGF antibody is also effective in inhibiting epidermal innervation and scratching in NC/Nga mouse (52). However, complete interception of NGF signaling may cause some side effects because autocrined NGF is thought to be involved in keratinocyte proliferation and important for normal elongation of neuronal fibers.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine Tumor Necrosis Factor-α Enhances Nerve Growth Factor Production in Human Keratinocytes, HaCaT Cells

Takaoka¹,

Shirai²,

Saito³

2009

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. The skin lesions of inflammatory skin diseases (e.g., atopic dermatitis or psoriasis) accompany infiltration of inflammatory cells like macrophages, where abnormal sensory innervations and elevation of nerve growth factor (NGF) level are observed. It is thought that increased NGF mediates the abnormal innervations and this may cause the hypersensitivity of the skin. However, the mechanism of this increased NGF production in the skin is still unknown. Here, we show that tumor necrosis factor (TNF)-α, but not interferon-γ or interleukin-6, enhanced the NGF production in human keratinocytes. The enhanced NGF production was abolished by both Raf-1 kinase and MEK inhibitors, whereas specific inhibitors of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase did not. The extracellular signal-regulated kinase (ERK) phosphorylation and expression of NGF mRNA were accelerated by TNF-α treatment. Furthermore, serum was necessary for the NGF production and epidermal growth factor could substitute for serum in the effect on NGF secretion. These results indicate that TNF-α enhances NGF production via the Raf-1 / MEK / ERK pathway in human keratinocytes, suggesting that regulating TNF-α is a therapeutic target to control NGF production and subsequent sensory innervations.

show abstract

Effects of Anti-Nerve Growth Factor Antibody on Symptoms in the NC/Nga Mouse, an Atopic Dermatitis Model

Cited by 81 publications

References 65 publications

An Update on Peripheral Mechanisms and Treatments of Itch

An Update on Peripheral Mechanisms and Treatments of Itch

Red Ginseng Inhibits Scratching Behavior Associated With Atopic Dermatitis in Experimental Animal Models

Inflammatory Cytokine Tumor Necrosis Factor-α Enhances Nerve Growth Factor Production in Human Keratinocytes, HaCaT Cells

Contact Info

Product

Resources

About