IL-1beta-induced production of metalloproteinases by synovial cells depends on gap junction conductance.
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-1beta (IL-1beta) and employed the assay to explore the biological function of gap junctions. IL-1beta produced a dose-dependent increase in MMP activity that was blocked by exposure to the gap junction inhibitors 18alpha-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-1beta signal transduction is critical to the process of cytokine-regulated secretion of MMPs by synovial cells.
Kolomytkin
Oleg V
OV
Department of Orthopaedic Surgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Marino
Andrew A
AA
Waddell
David D
DD
Mathis
J Michael
JM
Wolf
Robert E
RE
Sadasivan
Kalia K
KK
Albright
James A
JA
D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004594:Electrophysiology; D020536:Enzyme Activators / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D000442:Octanols / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D020536:Enzyme Activators; D007375:Interleukin-1; D000442:Octanols; D012333:RNA, Messenger; D003094:Collagen; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate; D006034:Glycyrrhetinic Acid