Doxycycline induces Fas/Fas ligand-mediated apoptosis in Jurkat T lymphocytes.
Tetracyclines have been used in the treatment of chronic inflammatory diseases associated with local infiltration of inflammatory cells and matrix destruction as observed in rheumatoid arthritis and periodontal disease. Fas/Fas ligand (FasL)-mediated apoptosis plays an important role in maintaining T lymphocyte homeostasis and modulating immune response. The present study demonstrates that doxycycline inhibits Jurkat T lymphocyte proliferation and induces apoptosis. The phytohemagglutinin (PHA)-activated Jurkat cells are more susceptible to doxycycline-induced apoptosis. Furthermore, doxycycline-induced apoptosis is associated with increased Fas/FasL expression in Jurkat cells. The increase of apoptosis in Jurkat cells treated with doxycycline is consistent with the increase of FasL expression. These results suggest that doxycycline may downregulate the inflammatory process in certain diseases by eliminating activated T lymphocytes through Fas/FasL-mediated apoptosis.
Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, 68198-3280, USA.
J
J
Liu
C A
CA
Kuszynski
B T
BT
Baxter
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology*; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D019014:fas Receptor / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D004318:Doxycycline