Modification of prostaglandin E2 and collagen synthesis in keratoconus fibroblasts, associated with an increase of interleukin 1 alpha receptor number.
Keratoconus, a bilateral corneal disease, is characterized by modifications in corneal shape and thinning of the stroma. It affects young people. From a biochemical point of view, a decrease in collagen content, probably due to the high collagenase activity, has been reported. In these experiments, we have studied the membrane receptors for interleukin 1 alpha, and the corresponding dissociation constant (KD). We also investigated synthesis of prostaglandin E2 (PGE2) and collagen, as well as kinetics of cyclooxygenase. Data from normal human corneas and from keratoconus were compared. Fibroblasts from keratoconus proved to bear four fold more IL1 binding sites than those from normal cornea, with similar KD. Both types of cells synthesize prostaglandin E2, even if IL1 is not added to the medium, but the keratoconus cells produce ten times more than the normal cornea cells. When the cells are stimulated with IL1, synthesis of PGE2 strongly increases and the amounts produced by keratoconus cells are always higher than those of the normal cornea cells. Kinetics of the cyclooxygenase show that Vmax. is 10 times higher in keratoconus than in normal cornea cells; Km's are the same. The amounts of collagen synthesized by keratoconus cells are slightly lower than those of normal cornea cells. Addition of IL1 to the cultures enhances synthesis of collagenase by the cells and decreases collagen found in the culture media. The drop of collagen is more important in keratoconus than in normal cornea cell cultures.
Bureau
J
J
Laboratoire de Recherche, Ophtalmologique, INSERM U 86, Hôtel-Dieu, Paris, France.
Fabre
E J
EJ
Hecquet
C
C
Pouliquen
Y
Y
Lorans
G
G
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003315:Cornea / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007640:Keratoconus / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000493:pharmacokinetics; D017472:Receptors, Interleukin-1 / Q000032:analysis*
D017472:Receptors, Interleukin-1; D003094:Collagen; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone