Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis

Toyoda, Masahiko; Nakamura, Motokazu; Makino, Teruhiko; Hino, Takayuki; Kagoura, Masayori; Morohashi, Masaaki

doi:10.1046/j.1365-2133.2002.04803.x

Cited by 298 publications

(214 citation statements)

References 70 publications

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“…However, several experimental studies have suggested an indirect pruritogenic effect of above cytokines via other mediators (55,58). Furthermore, hBDs and LL-37 elicited the expression or release of the most potent pruritogens, including substance P, PGE 2 , LTC 4 , and NGF (42,(59)(60)(61). These observations provide novel evidence that hBDs and LL-37 may participate in inflammatory and/or allergic reactions via the activation of mast cells.…”

Section: Discussionmentioning

confidence: 73%

Antimicrobial Peptides Human β-Defensins and Cathelicidin LL-37 Induce the Secretion of a Pruritogenic Cytokine IL-31 by Human Mast Cells

Niyonsaba

Ushio

Hara

et al. 2010

The Journal of Immunology

245

217

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In addition to their microbiocidal properties, human β-defensins (hBDs) and cathelicidin LL-37 stimulate a number of mammalian cell activities, including migration, proliferation, and cytokine/chemokine production. Because hBDs and LL-37 cause mast cells to release pruritogens such as histamine and PGs, we hypothesized that these peptides would stimulate the secretion of a novel pruritogenic mediator IL-31, predominantly produced by T cells. hBDs and LL-37 enhanced IL-31 gene expression and IL-31 protein production and release in the human mast cell line LAD2, as well as in peripheral blood-derived cultured mast cells, suggesting that mast cells are another source of IL-31. Moreover, the expression of IL-31 was elevated in psoriatic skin mast cells, and hBD-2–4 and LL-37, but not hBD-1, enhanced its expression in vivo in rat skin mast cells. hBDs and LL-37 also induced the release of other pruritogenic mediators, including IL-2, IL-4, IL-6, GM-CSF, nerve growth factor, PGE2, and leukotriene C4, and increased mRNA expression of substance P. hBD– and LL-37–mediated IL-31 production/release was markedly reduced by pertussis toxin and wortmannin, inhibitors of G-protein and PI3K, respectively. As evidenced by the inhibitory effects of MAPK-specific inhibitors, hBD-2–4 and LL-37 activated the phosphorylation of MAPKs p38, ERK, and JNK that were required for IL-31 production and release. The ability of hBDs and LL-37 to stimulate the production and release of IL-31 by human mast cells provides a novel mechanism by which skin-derived antimicrobial peptides/proteins may contribute to inflammatory reactions and suggests a central role of these peptides in the pathogenesis of skin disorders.

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Section: Discussionmentioning

confidence: 73%

Antimicrobial Peptides Human β-Defensins and Cathelicidin LL-37 Induce the Secretion of a Pruritogenic Cytokine IL-31 by Human Mast Cells

Niyonsaba

Ushio

Hara

et al. 2010

The Journal of Immunology

245

217

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“…NGF protein levels are increased in psoriatic skin compared to non-lesional and normal skin (14), and psoriatic keratinocytes express higher amounts of NGF than normal keratinocytes (15). Patients with atopic dermatitis also showed significant gains in NGF plasma levels compared to controls, and a strong correlation was noted between plasma NGF and severity of symptoms (16). These findings suggest that NGF may play an important role in the pathogenesis of atopic dermatitis, possibly regulating the development of atopic dermatitis lesions.…”

Section: Introductionmentioning

confidence: 69%

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

2005

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Abstract. Nerve growth factor (NGF) is an important substance in the skin, where it can modulate nerve maintenance and repair. However, the direct link between NGF and pruritic disease such as atopic dermatitis is not yet fully understood. To determine whether NGF plays a major role in atopic dermatitis and in the development or maintenance of skin lesions, we performed a study using NC / Nga mice and compared mice with and without skin lesions. Our examinations of the NC / Nga mice sought to detect nerve fibers in the epidermis, measured serum and skin NGF content, and observed skin NGF by immunohistochemistry staining. We also examined the effects of anti-NGF antibody on dermatitis symptoms in NC / Nga mice. In these mice, nerve fibers were significantly increased in the epidermis of lesioned skin, and the NGF content of the serum and skin was significantly elevated. Anti-NGF antibodies significantly inhibited the development and proliferation of skin lesions and epidermal innervation and significantly inhibited any growth in scratching but did not ameliorate scratching already developed. Our findings suggest that NGF plays important roles in the pathogenesis of atopic dermatitis-like skin lesions and that inhibiting the physiological effects of NGF or suppressing increased NGF production may prevent or even moderate the symptoms of atopic dermatitis.

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“…Recent studies have documented increased levels of nerve growth factor and substance P in plasma of AD patients which correlated positively with disease activity 22 . Brainderived growth factor, detected recently in sera and plasma of patients with AD, enhances the survival of eosinophils while increasing their chemotactic response in vitro 23 .…”

Section: ) Neuroimmunological Factorsmentioning

confidence: 99%

Atopic Dermatitis

2010

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Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis

Cited by 298 publications

References 70 publications

Antimicrobial Peptides Human β-Defensins and Cathelicidin LL-37 Induce the Secretion of a Pruritogenic Cytokine IL-31 by Human Mast Cells

Antimicrobial Peptides Human β-Defensins and Cathelicidin LL-37 Induce the Secretion of a Pruritogenic Cytokine IL-31 by Human Mast Cells

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

Atopic Dermatitis

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