Autocrine Induction of Substance P mRNA and Peptide in Cultured Normal Human Keratinocytes

Bae, Sang Jae; Matsunaga, Yoshitaka; Tanaka, Yoïchi; Katayama, Ichiro

doi:10.1006/bbrc.1999.1285

Cited by 46 publications

(39 citation statements)

References 25 publications

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“…2a). This dose dependency was very similar to keratinocytes [11]. Figure 5b shows the time course of expression of PPT-A mRNA in normal fibroblasts stimulated with exogenous SP (10 –8 M ).…”

Section: Resultssupporting

confidence: 68%

“…To confirm the presence of SP in normal fibroblasts, we performed immunohistochemical analysis, as shown in a previous study [11]. In short, normal human fibroblasts were cultured on chamber slide glass, stimulated with SP for 1.5 h, and then, the cells were washed with PBS(–) for several times.…”

Section: Resultsmentioning

confidence: 99%

“…In short, they were cultured to confluence and then stimulated with 10 –7 M of SP in fresh medium for 3 h and then washed with PBS(–) three times. SP immunostaining were obtained using rabbit antiserum (dilution 1:1,000) and then, the antibody-antigen complex was visualized with FITC-labeling immunoglobulin (dilution 1:30), as previously reported [11]. …”

Section: Methodsmentioning

confidence: 99%

“…In addition, SP precursor sequences are encoded by all 3 PPT-A mRNAs (α, β, χ). In our previous study, we reported that SP stimulated the cultured human-keratinocytes resulting in SP peptide induction and SP gene (β-PPT-A) expression in an autocrine fashion [11]. Parenti et al [12]reported that human fibroblasts expressed neurokinin (NK) receptor (specific SP receptor).…”

Section: Introductionmentioning

confidence: 99%

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Substance P Induced Preprotachykinin-A mRNA, Neutral Endopeptidase mRNA and Substance P in Cultured Normal Fibroblasts

Bae

Matsunaga

Takenaka

et al. 2002

Int Arch Allergy Immunol

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In certain skin diseases, stress can modulate the induction and/or progression of cutaneous manifestations. However, little is known about the circuit in neuroendocrine and in the immune systems of the skin. To address this question, we have analyzed the regulatory mechanisms of autocrine induction of substance P (SP) by cultured normal human fibroblasts that compose the major population of the skin and might augment stress-induced skin inflammatory responses. In nonstimulated conditions, normal fibroblasts express a moderate amount of preprotachykinin-A (PPT-A), a precursor of SP mRNA, and exogenous SP significantly upregulated PPT-A mRNA expression. Maximum response of SP peptide and SP mRNA in fibroblasts was observed 1–3 h after stimulation with SP. In contrast, the expression of neutral endopeptidase (NEP), a cell surface peptide with hydrolyzing activity of SP, was increased in fibroblasts stimulated with SP after 24 h. The administration of NEP inhibitor (phosphoramidon) to the fibroblasts induced higher SP production. In addition, the neurokinin (NK) receptor antagonists (spantide, FK224 and FK888) and protein synthesis inhibitor (cycloheximide) inhibited SP production by 30–40% of control response. In immunostaining study, specific cytoplasmic staining of SP was observed in fibroblasts stimulated with SP. Finally, we confirmed that the nucleotide sequence of the PPT-A expressed in fibroblasts perfectly corresponded to the gene bank human PPT-A cDNA. This is the first report that SP mRNA, NEP mRNA and SP peptide can be induced by normal human skin fibroblasts in response to exogenous SP, and that fibroblast-derived SP might play an important role in the induction and acceleration of certain cutaneous diseases.

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Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Substance P Induced Preprotachykinin-A mRNA, Neutral Endopeptidase mRNA and Substance P in Cultured Normal Fibroblasts

Bae

Matsunaga

Takenaka

et al. 2002

Int Arch Allergy Immunol

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show abstract

“…Furthermore, lamina propria macrophages obtained from the toxin A-injected ileal loops incubated in vitro with CP-96,345 had reduced TNF-␣ release, indicating an autocrine stimulation of SP in the cytokine secretion (9). Autocrine regulation of SP also has been suggested in other cell types (10)(11)(12). SP autocrine regulation in monocytederived macrophages (MDM) is further supported by the presence of specific cell membrane SP receptors (13) and production of SP protein by macrophages (8,9,(14)(15)(16)(17).…”

mentioning

confidence: 94%

Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes

Lai

Zhan

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The Brain in the Skin: Neuro-Epidermal Synapses

Boulais

Miséry

2009

Pruritus

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Autocrine Induction of Substance P mRNA and Peptide in Cultured Normal Human Keratinocytes

Cited by 46 publications

References 25 publications

Substance P Induced Preprotachykinin-A mRNA, Neutral Endopeptidase mRNA and Substance P in Cultured Normal Fibroblasts

Substance P Induced Preprotachykinin-A mRNA, Neutral Endopeptidase mRNA and Substance P in Cultured Normal Fibroblasts

Substance P antagonist (CP-96,345) inhibits HIV-1 replication in human mononuclear phagocytes

The Brain in the Skin: Neuro-Epidermal Synapses

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