Intravital imaging of IL-1beta production in skin

J Invest Dermatol. 2010 Jun;130(6):1571-80. doi: 10.1038/jid.2010.11. Epub 2010 Feb 11.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arthritis / chemically induced
  • Arthritis / metabolism
  • Arthritis / pathology
  • Cells, Cultured
  • Dermatitis, Contact / metabolism
  • Dermatitis, Contact / pathology
  • Disease Models, Animal
  • Interleukin-1beta / metabolism*
  • Lipopolysaccharides / adverse effects
  • Luminescent Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal / methods*
  • Oxazolone / adverse effects
  • Peritonitis / chemically induced
  • Peritonitis / metabolism
  • Peritonitis / pathology
  • Skin / cytology
  • Skin / metabolism*
  • Zymosan / adverse effects

Substances

  • Interleukin-1beta
  • Lipopolysaccharides
  • Luminescent Proteins
  • fluorescent protein 583
  • Oxazolone
  • Zymosan