IL-1beta -induced production of metalloproteinases by synovial cells depends on gap junction conductance

Departments of 1  Orthopaedic Surgery and 2  Cellular Biology and Anatomy and 3  Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130 Synovial cells can form networks connected by gap junctions. The purpose of this study...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2002-06, Vol.282 (6), p.C1254
Main Authors: Kolomytkin, Oleg V, Marino, Andrew A, Waddell, David D, Mathis, J. Michael, Wolf, Robert E, Sadasivan, Kalia K, Albright, James A
Format: Article
Language:English
Subjects:
Animals
Cell Line
Collagen - metabolism
Electrophysiology
Enzyme Activators - pharmacology
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - enzymology
Gap Junctions - drug effects
Gap Junctions - physiology
Glycyrrhetinic Acid - pharmacology
Interleukin-1 - pharmacology
Metalloendopeptidases - biosynthesis
Metalloendopeptidases - genetics
Octanols - pharmacology
Patch-Clamp Techniques
Rabbits
RNA, Messenger - metabolism
Signal Transduction - physiology
Synovial Membrane - cytology
Synovial Membrane - drug effects
Synovial Membrane - enzymology
Tetradecanoylphorbol Acetate - pharmacology
Time Factors
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Summary:Departments of 1  Orthopaedic Surgery and 2  Cellular Biology and Anatomy and 3  Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130 Synovial cells can form networks connected by gap junctions. The purpose of this study was to obtain evidence for a necessary role of gap junction intercellular communication in protein secretion by synovial cells. We developed a novel assay to measure the enzymatic activity of metalloproteinases (MMPs) produced by synovial cells in response to interleukin-1 (IL-1 ) and employed the assay to explore the biological function of gap junctions. IL-1 produced a dose-dependent increase in MMP activity that was blocked by exposure to the gap junction inhibitors 18 -glycyrrhetinic acid and octanol for as few as 50 min. The inhibitors produced an immediate and marked reduction in intercellular communication, as assessed by transient current analysis using the nystatin perforated-patch method. These observations suggest that communication through gap junctions early in IL-1 signal transduction is critical to the process of cytokine-regulated secretion of MMPs by synovial cells. perforated patch; HIG-82 cells; gap junction inhibitors; collagen assay
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.01166.2000