Biomaterial Database

Production of platelet-derived growth factor by interleukin-1 beta and transforming growth factor-beta-stimulated retinal pigment epithelial cells leads to contraction of collagen gels. 1997

P Choudhury, and W Chen, and R C Hunt

Department of Microbiology and Immunology, University of South Carolina School of Medicine, Columbia 29208, USA.

OBJECTIVE In an in vitro model of the later contractile stages of proliferative vitreoretinopathy, interleukin-1 beta (IL-1 beta) and transforming growth factor-beta (TGF-beta) stimulate the contraction of collagen gels by retinal pigment epithelial (RPE) cells. This contraction occurs after a lag period and appears not to be a direct effect of the cytokines but is mediated by another factor produced in the presence of the two cytokines. The nature of this factor has been investigated. METHODS Human RPE cells were seeded onto collagen gels in the presence of IL-1 beta and TGF-beta. After 24 hours, the conditioned medium was removed and added to new collagen gels seeded with RPE cells, and the diameter of the collagen gels was measured after various intervals. The ability of the conditioned medium to effect contraction was determined after various treatments, including size fractionation, heating, trypsin digestion, and binding to heparin-Sepharose. The involvement of platelet-derived growth factor (PDGF) as a stimulator of contraction was tested with neutralizing antibodies and by polymerase chain reaction analyses of specific mRNAs. RESULTS IL-1 beta and TGF-beta cause RPE cells to contract after a delay of up to 24 hours, whereas conditioned medium from cytokine-treated cells results in immediate contraction in a manner similar to that of serum. The factor in the conditioned medium causing immediate contraction was found to be heat-stable, trypsin-sensitive, and resistant to extremes of pH. It has a size of between 30 and 50 kDa and binds heparin. The factor in conditioned medium from cytokine-treated cells does not act in the presence of C-kinase inhibitors or cycloheximide, suggesting that signaling is mediated by way of protein kinase C and new protein synthesis. Stimulation of contraction by conditioned medium is inhibited by anti-PDGF antibodies, and contraction is stimulated by human PDGF. CONCLUSIONS Contraction in the presence of cytokines is mediated by the production of PDGF or a PDGF-like molecule. This factor could have implications in the pathogenesis of proliferative vitreoretinopathy.

UI	MeSH Term	Description	Entries
D007375	Interleukin-1	A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.	IL-1,Lymphocyte-Activating Factor,Epidermal Cell Derived Thymocyte-Activating Factor,Interleukin I,Macrophage Cell Factor,T Helper Factor,Epidermal Cell Derived Thymocyte Activating Factor,Interleukin 1,Lymphocyte Activating Factor
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D010857	Pigment Epithelium of Eye	The layer of pigment-containing epithelial cells in the RETINA; the CILIARY BODY; and the IRIS in the eye.	Eye Pigment Epithelium
D010982	Platelet-Derived Growth Factor	Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.	Platelet Derived Growth Factor,Factor, Platelet-Derived Growth,Growth Factor, Platelet-Derived
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D002846	Chromatography, Affinity	A chromatographic technique that utilizes the ability of biological molecules, often ANTIBODIES, to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Chromatography, Bioaffinity,Immunochromatography,Affinity Chromatography,Bioaffinity Chromatography
D003094	Collagen	A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).	Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D005782	Gels	Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.