Effects of increased concentrations of prostaglandin E levels with epidermolysis bullosa dystrophica recessive fibroblasts within a populated collagen lattice.
Tissue-cultured fibroblasts suspended in a collagen matrix actively reduce the size of that matrix by the process called lattice contraction. Cultured human fibroblasts derived from patients with epidermolysis bullosa dystrophica recessive (EBdr) cannot elongate and spread out when incorporated in a collagen matrix and they are therefore poor at contracting that collagen lattice. Culture medium from EBdr fibroblast-populated collagen lattice (FPCL) shows an increased concentration of prostaglandin, PGE2, compared with that in lattices made with equal numbers of normal human fibroblasts. The addition of the nonsteroid anti-inflammatory drug, indomethacin, to EBdr FPCL inhibits PGE synthesis, and promotes both cell elongation and spreading, as well as lattice contraction. However, the addition of indomethacin to normal FPCL does not stimulate either the spreading and elongation of cells or lattice contraction. PGE1 or PGE2 added to normal FPCL inhibits lattice contraction and cell elongation and spreading. Accordingly, EBdr FPCL does not undergo contraction due to altered elongation and spreading of fibroblasts, which process is related to enhanced PGE synthesis. It is proposed then that the contractile forces responsible for lattice contraction are identical to those responsible for the spreading and elongation of cells. Characteristic of EBdr fibroblasts are elevated levels of PGE2 which result in the failure of cells to spread and elongate within a collagen matrix. PGE2-treated normal cells do not readily spread and elongate and they do not readily contract FPCL.
D000527:Alprostadil; D002460:Cell Line; D003094:Collagen; D015232:Dinoprostone; D004820:Epidermolysis Bullosa / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis* / Q000494:pharmacology
D011458:Prostaglandins E; D003094:Collagen; D000527:Alprostadil; D015232:Dinoprostone; D007213:Indomethacin