The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi.
Tetracyclines moderate inflammatory responses of various etiologies. We hypothesized that tetracyclines, in addition to their antimicrobial function, could exert control over the inflammation elicited by Borrelia burgdorferi. To model systemic effects, we used the human monocytic cell line THP-1; to model effects in the central nervous system, we used rhesus monkey brain astrocytes and microglia. Cells were stimulated with live or sonicated B. burgdorferi or with the lipoprotein outer surface protein A in the presence of increasing concentrations of doxycycline or minocycline. Both antibiotics significantly reduced the production of tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8 in a dose-dependent manner in all cell types. Microarray analyses of the effect of doxycycline on gene transcription in spirochete-stimulated monocytes revealed that the NFKB and CHUK (alias, IKKA) genes were down-regulated. Functionally, phosphorylation of IkappaBalpha and binding of NF-kappaB to target DNA were both reduced in these cells. Our results suggest that tetracyclines may have a dual therapeutic effect in Lyme disease.
Bernardino
Andrea L F
AL
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA.
Kaushal
Deepak
D
Philipp
Mario T
MT
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D025065:Borrelia burgdorferi / Q000187:drug effects*; D001921:Brain / Q000166:cytology; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004318:Doxycycline / Q000627:therapeutic use*; D005091:Exons; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D008193:Lyme Disease / Q000188:drug therapy*; D008253:Macaca mulatta; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D008911:Minocycline / Q000627:therapeutic use*; D009000:Monocytes; D016328:NF-kappa B / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000187:drug effects / Q000302:isolation & purification; D015398:Signal Transduction / Q000187:drug effects
D000900:Anti-Bacterial Agents; D016328:NF-kappa B; D012313:RNA; D008911:Minocycline; D004318:Doxycycline