title: Interleukin-6 released from fibroblasts is essential for up-regulation of matrix metalloproteinase-1 expression by U937 macrophages in coculture: cross-talking between fibroblasts and U937 macrophages exposed to high glucose.
abstract: Matrix metalloproteinases (MMPs) play a key role in periodontal disease. Although it is known that macrophages and fibroblasts are co-localized and express MMPs in the diseased periodontal tissue, the effect of interaction between these two cell types on MMP expression has not been well elucidated. Furthermore although it is known that diabetes is associated with accelerated periodontal tissue destruction, it remains unknown whether hyperglycemia, a major metabolic abnormality in diabetes, regulates MMP expression by affecting the cross-talking between fibroblasts and macrophages. In this study, human gingival fibroblasts and U937 macrophages were cocultured in a two-compartment transwell culture system, and the cells were treated with normal or high glucose. We found that coculture of fibroblasts and U937 macrophages led to an augmentation of MMP-1 expression by U937 macrophages, and high glucose further enhanced this augmentation. Similar observations were also made in the coculture of fibroblasts and human primary monocytes. We also found that interleukin 6 (IL-6) released by fibroblasts was essential for the augmentation of MMP-1 expression by U937 macrophages. Furthermore our results showed that high glucose, IL-6, and lipopolysaccharide had a synergistic effect on MMP-1 expression. Finally our study indicated that MAPK pathways and activator protein-1 transcription factor were involved in the coculture- and high glucose-augmented MMP-1 expression. In conclusion, this study demonstrates that IL-6 derived from fibroblasts is essential for MMP-1 up-regulation by cross-talking between fibroblasts and U937 macrophages exposed to high glucose, revealing an IL-6-dependent mechanism in MMP-1 up-regulation.
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Kamala P
authors.initials: KP
authors.lastname: Sundararaj
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Devadoss J
authors.initials: DJ
authors.lastname: Samuvel
authors.affiliation: Division of Endocrinology, Diabetes, and Medical Genetics, Department of Medicine Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Stomatology, College of Dental Medicine, Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sanders
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center Medical University of South Carolina, Charleston, South Carolina 29425; Division of Endocrinology, Diabetes, and Medical Genetics, Department of Medicine Medical University of South Carolina, Charleston, South Carolina 29425.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.affiliation: Ralph H. Johnson Veterans Affairs Medical Center Medical University of South Carolina, Charleston, South Carolina 29425; Division of Endocrinology, Diabetes, and Medical Genetics, Department of Medicine Medical University of South Carolina, Charleston, South Carolina 29425. Electronic address: huangyan@musc.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D018920:Coculture Techniques; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000819:agonists / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000819:agonists / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D013549:Sweetening Agents / Q000494:pharmacology*; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013549:Sweetening Agents; D020781:Matrix Metalloproteinase 1; D005947:Glucose