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Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin

Journal Article · · Experimental Cell Research
 [1]; ; ;  [1];  [2];  [1];  [3];  [4];  [3]
  1. Department of Biomedical Sciences for Health, Università degli Studi di Milano, 20133 Milan (Italy)
  2. Department of Experimental and Clinical Medicine, Università degli Studi di Firenze, 50125 Florence (Italy)
  3. Department of Surgery and Translational Medicine, Università degli Studi di Firenze, 50125 Florence (Italy)
  4. I.R.C.C.S. Istituto Ortopedico Galeazzi, 20161 Milan (Italy)
Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72) h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.
OSTI ID:
22648600
Journal Information:
Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 345; ISSN 0014-4827; ISSN ECREAL
Country of Publication:
United States
Language:
English

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