K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis

An in vivo study using the severe combined immunodeficient mouse-human skin model

Siba P Raychaudhuri, Mrinmoy Sanyal, Helena Weltman, Smriti Kundu-Raychaudhuri

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The peripheral nervous system, in addition to its sensory and motor functions, can induce a local inflammatory response known as neurogenic inflammation. This phenomenon plays a critical role in several inflammatory diseases, e.g., asthma, atopy, rheumatoid arthritis, psoriasis, and ulcerative colitis. Neurogenic inflammation and the role of nerve growth factor (NGF) have been extensively studied in psoriasis. There are increased levels of NGF in the keratinocytes and upregulation of NGF receptor (NGF-R) in the cutaneous nerves of psoriatic plaques. NGF can influence all the salient pathologic events noticed in psoriasis such as proliferation of keratinocytes, angiogenesis, T cell activation, expression of adhesion molecules, proliferation of cutaneous nerves, and upregulation of neuropeptides. In this double-blinded, placebo-controlled study, we addressed the role of NGF/NGF-R in psoriasis in an in vivo system using the severe combined immunodeficient (SCID) mouse-human skin model of psoriasis. The transplanted psoriatic plaques on the SCID mice (n = 12) were treated with K252a, a high-affinity NGF receptor blocker. Psoriasis significantly improved following 2 wk of therapy. The length of the rete pegs changed from 308.57 ± 98.72 to 164.64 ± 46.78 μm (p < 0.01, Student's t test). A similar improvement of psoriasis was observed by directly inhibiting NGF with NGF-neutralizing antibody. NGF-neutralizing antibody in normal saline at 10 ng (n = 4) and 20 ng (n = 4) per kilogram of body weight doses were used. Both doses of NGF-neutralizing antibody reduced rete peg lengths significantly, e.g., from 298.5 ± 42.69 to 150.52 ± 32.93 μm (p < 0.05, Student's t test). This study provides evidence for the role of NGF and its high-affinity receptor in the pathogenesis of psoriasis and insights to develop novel therapeutic modalities.

Original languageEnglish (US)
Pages (from-to)812-819
Number of pages8
JournalJournal of Investigative Dermatology
Volume122
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Fingerprint

Nerve Growth Factor Receptor
SCID Mice
Nerve Growth Factor
Psoriasis
Skin
Neutralizing Antibodies
Neurogenic Inflammation
Keratinocytes
Up-Regulation
staurosporine aglycone
Students
T-cells
Peripheral Nervous System
Neurology
Neuropeptides
Ulcerative Colitis
Rheumatoid Arthritis
Adhesion
Asthma
Chemical activation

ASJC Scopus subject areas

  • Dermatology

Cite this

K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis : An in vivo study using the severe combined immunodeficient mouse-human skin model. / Raychaudhuri, Siba P; Sanyal, Mrinmoy; Weltman, Helena; Kundu-Raychaudhuri, Smriti.

In: Journal of Investigative Dermatology, Vol. 122, No. 3, 03.2004, p. 812-819.

Research output: Contribution to journalArticle

@article{837e013a17bb4ee1a1b498ce52d71156,
title = "K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis: An in vivo study using the severe combined immunodeficient mouse-human skin model",
abstract = "The peripheral nervous system, in addition to its sensory and motor functions, can induce a local inflammatory response known as neurogenic inflammation. This phenomenon plays a critical role in several inflammatory diseases, e.g., asthma, atopy, rheumatoid arthritis, psoriasis, and ulcerative colitis. Neurogenic inflammation and the role of nerve growth factor (NGF) have been extensively studied in psoriasis. There are increased levels of NGF in the keratinocytes and upregulation of NGF receptor (NGF-R) in the cutaneous nerves of psoriatic plaques. NGF can influence all the salient pathologic events noticed in psoriasis such as proliferation of keratinocytes, angiogenesis, T cell activation, expression of adhesion molecules, proliferation of cutaneous nerves, and upregulation of neuropeptides. In this double-blinded, placebo-controlled study, we addressed the role of NGF/NGF-R in psoriasis in an in vivo system using the severe combined immunodeficient (SCID) mouse-human skin model of psoriasis. The transplanted psoriatic plaques on the SCID mice (n = 12) were treated with K252a, a high-affinity NGF receptor blocker. Psoriasis significantly improved following 2 wk of therapy. The length of the rete pegs changed from 308.57 ± 98.72 to 164.64 ± 46.78 μm (p < 0.01, Student's t test). A similar improvement of psoriasis was observed by directly inhibiting NGF with NGF-neutralizing antibody. NGF-neutralizing antibody in normal saline at 10 ng (n = 4) and 20 ng (n = 4) per kilogram of body weight doses were used. Both doses of NGF-neutralizing antibody reduced rete peg lengths significantly, e.g., from 298.5 ± 42.69 to 150.52 ± 32.93 μm (p < 0.05, Student's t test). This study provides evidence for the role of NGF and its high-affinity receptor in the pathogenesis of psoriasis and insights to develop novel therapeutic modalities.",
author = "Raychaudhuri, {Siba P} and Mrinmoy Sanyal and Helena Weltman and Smriti Kundu-Raychaudhuri",
year = "2004",
month = "3",
doi = "10.1111/j.0022-202X.2003.12602.x",
language = "English (US)",
volume = "122",
pages = "812--819",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis

T2 - An in vivo study using the severe combined immunodeficient mouse-human skin model

AU - Raychaudhuri, Siba P

AU - Sanyal, Mrinmoy

AU - Weltman, Helena

AU - Kundu-Raychaudhuri, Smriti

PY - 2004/3

Y1 - 2004/3

N2 - The peripheral nervous system, in addition to its sensory and motor functions, can induce a local inflammatory response known as neurogenic inflammation. This phenomenon plays a critical role in several inflammatory diseases, e.g., asthma, atopy, rheumatoid arthritis, psoriasis, and ulcerative colitis. Neurogenic inflammation and the role of nerve growth factor (NGF) have been extensively studied in psoriasis. There are increased levels of NGF in the keratinocytes and upregulation of NGF receptor (NGF-R) in the cutaneous nerves of psoriatic plaques. NGF can influence all the salient pathologic events noticed in psoriasis such as proliferation of keratinocytes, angiogenesis, T cell activation, expression of adhesion molecules, proliferation of cutaneous nerves, and upregulation of neuropeptides. In this double-blinded, placebo-controlled study, we addressed the role of NGF/NGF-R in psoriasis in an in vivo system using the severe combined immunodeficient (SCID) mouse-human skin model of psoriasis. The transplanted psoriatic plaques on the SCID mice (n = 12) were treated with K252a, a high-affinity NGF receptor blocker. Psoriasis significantly improved following 2 wk of therapy. The length of the rete pegs changed from 308.57 ± 98.72 to 164.64 ± 46.78 μm (p < 0.01, Student's t test). A similar improvement of psoriasis was observed by directly inhibiting NGF with NGF-neutralizing antibody. NGF-neutralizing antibody in normal saline at 10 ng (n = 4) and 20 ng (n = 4) per kilogram of body weight doses were used. Both doses of NGF-neutralizing antibody reduced rete peg lengths significantly, e.g., from 298.5 ± 42.69 to 150.52 ± 32.93 μm (p < 0.05, Student's t test). This study provides evidence for the role of NGF and its high-affinity receptor in the pathogenesis of psoriasis and insights to develop novel therapeutic modalities.

AB - The peripheral nervous system, in addition to its sensory and motor functions, can induce a local inflammatory response known as neurogenic inflammation. This phenomenon plays a critical role in several inflammatory diseases, e.g., asthma, atopy, rheumatoid arthritis, psoriasis, and ulcerative colitis. Neurogenic inflammation and the role of nerve growth factor (NGF) have been extensively studied in psoriasis. There are increased levels of NGF in the keratinocytes and upregulation of NGF receptor (NGF-R) in the cutaneous nerves of psoriatic plaques. NGF can influence all the salient pathologic events noticed in psoriasis such as proliferation of keratinocytes, angiogenesis, T cell activation, expression of adhesion molecules, proliferation of cutaneous nerves, and upregulation of neuropeptides. In this double-blinded, placebo-controlled study, we addressed the role of NGF/NGF-R in psoriasis in an in vivo system using the severe combined immunodeficient (SCID) mouse-human skin model of psoriasis. The transplanted psoriatic plaques on the SCID mice (n = 12) were treated with K252a, a high-affinity NGF receptor blocker. Psoriasis significantly improved following 2 wk of therapy. The length of the rete pegs changed from 308.57 ± 98.72 to 164.64 ± 46.78 μm (p < 0.01, Student's t test). A similar improvement of psoriasis was observed by directly inhibiting NGF with NGF-neutralizing antibody. NGF-neutralizing antibody in normal saline at 10 ng (n = 4) and 20 ng (n = 4) per kilogram of body weight doses were used. Both doses of NGF-neutralizing antibody reduced rete peg lengths significantly, e.g., from 298.5 ± 42.69 to 150.52 ± 32.93 μm (p < 0.05, Student's t test). This study provides evidence for the role of NGF and its high-affinity receptor in the pathogenesis of psoriasis and insights to develop novel therapeutic modalities.

UR - http://www.scopus.com/inward/record.url?scp=1842689793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1842689793&partnerID=8YFLogxK

U2 - 10.1111/j.0022-202X.2003.12602.x

DO - 10.1111/j.0022-202X.2003.12602.x

M3 - Article

VL - 122

SP - 812

EP - 819

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 3

ER -