title: Hyperkeratosis in human lower limb lymphedema: the effect of stagnant tissue fluid/lymph.
abstract: BACKGROUND
  Hyperkeratosis of skin in lower limb lymphedema is one of the sequelae of tissue fluid/lymph (TF/L) stasis, but its mechanisms remain unknown. It is noteworthy, nonetheless, that human TF/L contains high levels of growth factors and cytokines, and may serve as the physiological environment for keratinocyte (KC) proliferation.
  
  
  OBJECTIVE
  The aim of the study was to investigate the effect of human TF/L on human KC proliferation, differentiation and on the expression of epidermal stem cell markers on them.
  
  
  METHODS
  KC were isolated from lymphedema and normal skin, and cultured for 1-14 days in TF/L with neutralized Interleukin 1β, Interleukin 6, tumour necrosis factor α (TNF-α), keratinocyte growth factor (KGF) or tumour growth factor β (TGF-β). Alternatively, KC receptors for these factors were blocked.
  
  
  RESULTS
  The number of KC cultured in TF/L was increased, as was the percentage of mitotic figures. There was a higher percentage of p63, CD29, Ki67, PCNA, CK6, CK17, CK16 and a lower of CK10, CK14, filaggrin and involucrin-positive KC. Neutralization of TF/L IL-1β, IL-6, TNF-α and KGF as well as blockage of their receptors resulted in decreased percentage of mitotic KC. TGF-β had a limited effect on KC proliferation.
  
  
  CONCLUSIONS
  Hyperkeratosis in lymphedema may be the effect of a high concentration of cytokines in the stagnant TF/L tissue, but not because of presumed changes in the KC.
authors: Department of Transplantation Surgery and Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors: A
authors: A
authors: Domaszewska-Szostek
authors: Department of Transplantation Surgery and Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors: M
authors: M
authors: Zaleska
authors: Department of Transplantation Surgery and Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.|Department of Transplantation and Vascular Surgery, Central Clinical Hospital, Ministry of Internal Affairs, Warsaw, Poland.
authors: W L
authors: WL
authors: Olszewski
mesh_terms: D001826:Body Fluids; D000091344:Filaggrin Proteins; D006801:Humans; D007642:Keratosis / Q000150:complications*; D007866:Leg; D008209:Lymphedema / Q000150:complications*