Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. nnakai@koto.kpu-m.ac.jp

BACKGROUND AND OBJECTIVE: The expression of nerve growth factor (NGF) is known to increase in the skin of patients with atopic dermatitis (AD) and is related to disease aggravation. In the present study, we measured skin NGF levels in AD patients and determined whether they correlate to AD severity as well as treatment effects. METHODS: NGF in the horny layer (horn NGF) of skin lesions found on the cubital fossa of AD patients was collected via tape stripping and measured using ELISA before and after 2 and 4 weeks following initiation of treatments. Itching and eruptions on the lesions were also evaluated. Peripheral blood eosinophil count, serum LDH level and total serum IgE level were also examined. RESULTS: The level of NGF was significantly higher in AD patients than in healthy controls, and correlated with the severity of itch, erythema, scale/xerosis, eosinophil count, and LDH level. The NGF level decreased significantly at 2 and 4 weeks of treatment with olopatadine, a histamine H(1) receptor antagonist, and/or topical steroid. The reduction in NGF correlated with the decrease in the severity of itching and erythema, papule, scale/xerosis and lichenification of the lesion, eosinophil count, and LDH level. In psoriatic lesional skin with itch, the horn NGF was significantly higher than in non-lesional skin of psoriasis, but the value was lower than NGF in atopic skin. CONCLUSIONS: The level of horn NGF was found to reflect the severity of itching and eruptions in AD. Therefore, quantification of NGF in the samples collected directly from the horny layer appears to be useful in assessing severity and therapeutic effects in AD. PMID: 18922683 [PubMed - indexed for MEDLINE]

Induction of nerve growth factor synthesis by sphingomyelinase and ceramide in primary astrocyte cultures.

Galve-Roperh I, Haro A, Díaz-Laviada I.

Dpto. Bioquímica y Biología Molecular I, Facultad de Biología, Universidad Complutense, Madrid, Spain.

Astrocytes synthesize nerve growth factor (NGF) in response to pro-inflammatory cytokines. To further study the signaling mechanism involved in this induction of NGF production, the sphingomyelin (SM) pathway was studied. Addition of exogenous neutral SMase (Staphylococcus aureus) or C2-ceramide to primary cultures of newborn rat cortical astrocytes elicited a dose-response increase of NGF synthesis, with maximal effect at 1 U/ml and 25 microM, respectively. Induction of NGF synthesis by SMase and ceramide was shown to be independent of classical PKC activity. Intracellular cAMP-raising agents, such as forskolin and 3-isobutyl-1-methylxanthine, partially prevented the SMase- and C2-ceramide-induced secretion of NGF to the cell supernatant. PD098059 and apigenin, inhibitors of the mitogen-activated protein (MAP) kinase pathway, produced a dose-response inhibition of the SMase- and C2-cer-induced release of NGF. This observation points to the possibility that regulation of NGF synthesis and secretion by the SMase pathway may be mediated downstream by the MAP kinase cascade. As a matter of fact, pre-treatment of astrocytes with SMase or C8-ceramide led to an increased phosphorylation of raf-1. Moreover, MAP kinase activity was enhanced in astrocytes treated with SMase or both ceramides. In conclusion, results suggest that the SMase pathway may control NGF synthesis in the central nervous system, and raise the possibility of an involvement of the MAP kinase cascade in this process. PMID: 9450681 [PubMed - indexed for MEDLINE]

Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and psoriasis horny layer and effect of treatment on NGF in atopic dermatitis.

Induction of nerve growth factor synthesis by sphingomyelinase and ceramide in primary astrocyte cultures.