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Am J Physiol Cell Physiol (January 30, 2002). doi:10.1152/ajpcell.01166.2000
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Articles in PresS, published online ahead of print January 9, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.01166.2000
Submitted on August 18, 2000
Accepted on January 3, 2002

IL-1ß-induced production of metalloproteinases by synovial cells depends on gap-junction conductance during the early stage of signal transduction

Oleg V Kolomytkin1, Andrew A Marino1*, Kalia K Sadasivan1, Robert E Wolf2, David D Waddell1, and James A Albright1

1 Orthopaedic Surgery, LSU Health Sciences Center, Shreveport, Louisiana, USA
2 Center of Excellence for Arthritis and Rheumatology, LSU Health Sciences Center, Shreveport, Louisiana, USA

* To whom correspondence should be addressed. E-mail: amarino{at}lsumc.edu.

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-1ß (IL-1ß), and employed the assay to explore the biological function of gap junctions. IL-1ß produced a dose-dependent increase in MMP activity that was blocked by exposure to the gap-junction inhibitors 18{alpha}-glycyrrhetinic acid and octanol for as few as 50 minutes. 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 occurring early in IL-1ß signal transduction was critical to the process of cytokine-regulated secretion of MMPs by synovial cells.




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