Psoriasis and Altered Calcium Metabolism: Downregulated Capacitative Calcium Influx and Defective Calcium-Mediated Cell Signaling in Cultured Psoriatic Keratinocytes1

Seija-Liisa Karvonen,*2 Timo Korkiama ki,*2 Heli Yla -Outinen,* Marja Nissinen,* Harri Teerikangas,:j Kati Pummi,§ Jaakko Karvonen,t and Juha Peltonen*

*Department of Anatomy and Cell Biology, tDepartment of Dermatology, and :jDepartment of 
Surgery, University of Oulu, Oulu, Finland; §Department of Medical Biochemistry, University of Turku, Turku, Finland; <Department of  Dermatology, University Hospital of Tampere, Tampere, Finland

 

Intracellular calcium plays an important part in the regulation of proliferation and differentiation of keratinocytes. Detached from their in vivo environment, cultured psoriatic keratinocytes were investigated by monitoring free intracellular calcium concentration, which was measured using fura-2/AM as a calcium-sensitive probe. The mean increase in intracellular calcium of psoriatic keratinocytes was significantly reduced compared with control keratinocytes when intracellular calcium stores were mobilized from endoplasmic reticulum with thapsigargin. This
find- ing suggests defective capacitative calcium influx of psoriatic cells. Intracellular calcium stores were simi- lar in psoriatic and control keratinocytes, when extracellular calcium was chelated with ethylenegly-col-bis(β-aminoethyl ether)-N,N,N’,N’,-tetraacetic acid and intracellular calcium was depleted with thapsigargin. Mechanical wounding of keratinocyte monolayer resulted in a significantly reduced rise in intracellular calcium of psoriatic cells in low (< 0.1 mM) and high (1.8 mM) extracellular calcium suggesting defective intercellular coupling of psoriatic keratinocytes. Blocking of gap-junctions with heptanol in wounded keratinocytes did not affect the intracellular calcium response in psoriatic keratino- cytes in contrast to healthy keratinocytes. Adding adenosine triphosphate to culture medium resulted in a more pronounced intracellular calcium increase than thapsigargin in psoriatic keratinocytes, suggest-
ing that inositol triphosphate-mediated, P2-puriner- gic signaling was enhanced in these cells. Moreover, psoriatic keratinocytes maintained their defective responses up to at least fifth passage suggesting that psoriatic keratinocytes have an inborn error in cal- cium metabolism, rather than a localized defect in response to altered extracellular calcium gradient observed in vivo. Key words: keratinocyte cultures/intra- cellular calcium/gap-junctions/P2-purinergic receptors. ] Invest Dermatol 114:693-700, 2000