Staphylococcal enterotoxin B causes proliferation of sensory C-fibers and subsequent enhancement of neurogenic inflammation in rat skin.
BACKGROUND
Staphylococcal enterotoxin B (SEB) may be associated with the exacerbation of atopic dermatitis. We investigated whether SEB causes proliferation of sensory C-fibers and subsequent enhancement of plasma leakage induced by sensorineural stimulation in rat skin.


METHODS
SEB was applied intracutaneously to the abdomen of preweaning and adult rats. Evans blue dye leakage into the skin induced by topical 10% formalin was measured as an index of neurogenic skin vascular permeability. Local expression of substance P, tachykinin NK1 receptors, and nerve growth factor was assessed immunohistochemically. In addition, we assessed the effects of topical tacrolimus on these skin responses induced by SEB.


RESULTS
Increased neurogenic skin plasma leakage was seen 7 days after SEB treatment in 2 different age groups. Innervation of substance P-immunoreactive nerves and expression of tachykinin NK1 receptors and nerve growth factor were also promoted by SEB, peaking at 7 days, 7 days, and 56 h after SEB treatment, respectively. Tacrolimus markedly inhibited these skin changes.


CONCLUSIONS
SEB increased the innervation of sensory C-fibers and tachykinin NK1 receptors in rat skin, probably because of upregulated production of neurotrophins, including nerve growth factor, leading to enhancement of neurogenic skin inflammation. T cell activation induced by SEB may initiate these changes.
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mihoko
M
Ohshima
Mio
M
Miyake
Masanori
M
Takeda
Michihiro
M
Kamijima
Tatsuo
T
Sakamoto
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D005447:Fluocinonide / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000473:pathology; D020932:Nerve Growth Factor / Q000032:analysis; D020078:Neurogenic Inflammation / Q000209:etiology* / Q000473:pathology; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000294:innervation / Q000473:pathology*; D013047:Specific Pathogen-Free Organisms; D013373:Substance P / Q000032:analysis; D050916:TRPV Cation Channels / Q000032:analysis; D016559:Tacrolimus / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D004768:Enterotoxins; D007166:Immunosuppressive Agents; D018040:Receptors, Neurokinin-1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D005447:Fluocinonide; D013373:Substance P; C031818:enterotoxin B, staphylococcal; D020932:Nerve Growth Factor; D016559:Tacrolimus
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