PMID- 21054185 OWN - NLM STAT- MEDLINE DCOM- 20110321 LR - 20151119 IS - 1557-7732 (Electronic) IS - 1080-7683 (Linking) VI - 26 IP - 6 DP - 2010 Dec TI - Effect of infliximab on tumor necrosis factor-alpha-induced alterations in retinal microvascular endothelial cells and retinal pigment epithelial cells. PG - 549-56 LID - 10.1089/jop.2010.0079 [doi] AB - PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) may disrupt the extracellular matrix components comprising the blood-retinal barrier (BRB) in patients with posterior uveitis, such as Behcet's disease. We investigated changes in the mRNA expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human BRB cells in the presence of TNF-alpha in vitro and examined the effect of infliximab addition. METHODS: Cells were cultured in the presence or absence of TNF-alpha, and TNF-alpha-exposed cells were treated with or without infliximab. We measured the expression levels of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 mRNA in human retinal microvascular endothelial ACBRI181 cells and retinal pigment epithelial ARPE-19 cells by real-time polymerase chain reaction. The cell-derived proteins degraded by MMP were observed after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: Expression of MMP-3 increased and TIMP-1 decreased in the presence of 10 ng/mL TNF-alpha in ACBRI181 cells. Expression of MMP-1 increased and TIMP-2 decreased in the presence of 10 ng/mL TNF-alpha in ARPE-19 cells. These altered levels of expression were reversed by the addition of infliximab. The cell-derived proteins degraded by MMP-1 and -3 were detected in each set of cells. CONCLUSIONS: The presence of TNF-alpha altered expression of MMPs and TIMPs in cells comprising the BRB, and infliximab counteracted this alteration. FAU - Li, Huili AU - Li H AD - Department of Ophthalmology, Aichi Medical University, Aichi, Japan. FAU - Yoneda, Masahiko AU - Yoneda M FAU - Takeyama, Masayuki AU - Takeyama M FAU - Sugita, Iichiro AU - Sugita I FAU - Tsunekawa, Hinako AU - Tsunekawa H FAU - Yamada, Hiroshi AU - Yamada H FAU - Watanabe, Daisuke AU - Watanabe D FAU - Mukai, Tomoyuki AU - Mukai T FAU - Yamamura, Masahiro AU - Yamamura M FAU - Iwaki, Masayoshi AU - Iwaki M FAU - Zako, Masahiro AU - Zako M LA - eng PT - Journal Article DEP - 20101105 PL - United States TA - J Ocul Pharmacol Ther JT - Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics JID - 9511091 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antibodies, Monoclonal) RN - 0 (RNA, Messenger) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - B72HH48FLU (Infliximab) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Anti-Inflammatory Agents/*pharmacology MH - Antibodies, Monoclonal/*pharmacology MH - Blood-Retinal Barrier/*drug effects/metabolism MH - Cell Line MH - Electrophoresis, Polyacrylamide Gel MH - Endothelial Cells/drug effects/metabolism MH - Endothelium, Vascular/drug effects/metabolism MH - Gene Expression Regulation/*drug effects MH - Humans MH - Infliximab MH - Matrix Metalloproteinases/metabolism MH - Polymerase Chain Reaction MH - RNA, Messenger/metabolism MH - Retinal Pigment Epithelium/drug effects/metabolism MH - Retinal Vessels/drug effects/metabolism MH - Tissue Inhibitor of Metalloproteinase-1/drug effects/metabolism MH - Tissue Inhibitor of Metalloproteinase-2/drug effects/metabolism MH - Tumor Necrosis Factor-alpha/administration & dosage/*metabolism EDAT- 2010/11/09 06:00 MHDA- 2011/03/22 06:00 CRDT- 2010/11/09 06:00 PHST- 2010/11/09 06:00 [entrez] PHST- 2010/11/09 06:00 [pubmed] PHST- 2011/03/22 06:00 [medline] AID - 10.1089/jop.2010.0079 [doi] PST - ppublish SO - J Ocul Pharmacol Ther. 2010 Dec;26(6):549-56. doi: 10.1089/jop.2010.0079. Epub 2010 Nov 5.