Interleukin-1alpha downregulates extracellular-superoxide dismutase in human corneal keratoconus stromal cells.
OBJECTIVE
The purpose of this investigation was to elucidate the regulation of corneal extracellular superoxide dismutase (SOD3) synthesis in keratoconus. We compared the basal and cytokine-regulated SOD3 synthesis in cultured human stromal cells from keratoconus corneas to stromal cells from normal and bullous keratopathy corneas.


METHODS
Keratocyte cultures were obtained from patients undergoing corneal transplantation for keratoconus and bullous keratopathy, and from healthy donor corneas. The cell lines obtained were cultured until near confluence and interleukin-1alpha, interleukin-6, transforming growth factor beta, or platelet derived growth factor were added to the media. The phenotypes of the cultured cells were assessed by immunocytochemical expression of alpha-smooth muscle actin and CD34. SOD3 protein contents were determined in the culture media with ELISA after 24, 48, 72, and 96 h.


RESULTS
Interleukin-1alpha had an inhibitory effect on SOD3 synthesis exclusively in the keratoconus cultures (p<0.01). Platelet derived growth factor induced a reduction in SOD3 synthesis in all groups (p<0.05).


CONCLUSIONS
Here, we demonstrate that cultured keratoconus stromal cells respond with a reduced SOD3 synthesis to interleukin-1alpha, which is not the case in corresponding normal or bullous keratopathy cells. Since interleukin-1alpha is upregulated in corneal trauma and inflammation, keratoconus corneas may muster an insufficient oxidative defense under such conditions.
Olofsson
Eva M
EM
Department of Clinical Sciences/Ophthalmology, Section for Anatomy, Umeå University, Sweden.
Marklund
Stefan L
SL
Pedrosa-Domellöf
Fatima
F
Behndig
Anders
A
D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003319:Corneal Stroma / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D053582:Interleukin-1alpha / Q000494:pharmacology*; D007640:Keratoconus / Q000201:enzymology* / Q000473:pathology*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000378:metabolism*
D053582:Interleukin-1alpha; C441642:SOD3 protein, human; D013482:Superoxide Dismutase