Intravital imaging of IL-1beta production in skin.
IL-1 is a prototypic inflammatory cytokine that has pathogenic roles in various skin disorders. Although Langerhans cells (LCs) have been reported to express IL-1beta mRNA upon application of contact sensitizers, it remains unclear whether other cell types produce IL-1beta in skin. Thus, we sought to directly identify IL-1beta-producing cells in living animals by construction of transgenic mice expressing DsRed fluorescence protein gene under the control of IL-1beta promoter. Little DsRed fluorescence signal was detected in skin under steady-state conditions. Striking increases in DsRed signal were observed after topical application of a contact sensitizer, oxazolone, which also induced markedly elevated IL-1beta mRNA and protein expression. DsRed signal was expressed primarily by CD45(+)/CD11b(+) myeloid leukocytes in both epidermal and dermal compartments and was detected only in small fractions of epidermal LCs. Interestingly, DsRed(+) cells emerged preferentially as clusters around hair follicles. Intravital confocal imaging experiments revealed highly motile potentials of DsRed(+) cells-they constantly crawled around hair follicles via amoeba-like movements with a mean velocity of 1.0+/-0.4 microm min(-1) (epidermis) or 2.7+/-1.4 microm min(-1) (dermis). The newly developed in vivo imaging system represents a useful tool for studying spatial regulation of IL-1beta production in skin.
Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, 3000 Arlington Avenue, Toledo, OH 43614, USA.
Hironori
H
Matsushima
Yasushi
Y
Ogawa
Toru
T
Miyazaki
Hiroaki
H
Tanaka
Akiko
A
Nishibu
Akira
A
Takashima
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008164:Luminescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods*; D010081:Oxazolone / Q000009:adverse effects; D010538:Peritonitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D015054:Zymosan / Q000009:adverse effects
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008164:Luminescent Proteins; C413663:fluorescent protein 583; D010081:Oxazolone; D015054:Zymosan