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Amphotericin B up-regulates lipid A-induced IL-6 production via caspase-8

R Tamai1, M Sugamata, Y Kiyoura

  • 1Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.

Journal of Dental Research
|April 28, 2012
PubMed

Insights

Amphotericin B enhances the inflammatory response to bacterial components like lipid A. This interaction, dependent on cell membrane cholesterol, involves caspase-8 and may be mitigated by prior periodontal treatment.

Area of Science:

  • Immunology
  • Pharmacology
  • Microbiology

Background:

  • Amphotericin B, an antifungal, can stimulate pro-inflammatory cytokines.
  • Lipid A from Gram-negative bacteria is a potent immune activator.

Purpose of the Study:

  • To investigate how amphotericin B affects lipid A-induced cytokine production.
  • To explore the mechanisms underlying this synergistic effect.

Main Methods:

  • Human gingival fibroblasts were treated with amphotericin B and lipid A.
  • Levels of interleukin (IL)-6, IL-8, and nuclear factor (NF)-κB activation were measured.
  • The role of cholesterol-rich microdomains and caspase-8 was assessed using methyl-β-cyclodextrin and inhibitors.

Main Results:

  • Amphotericin B alone caused minor IL-6 and IL-8 increases.
  • It synergistically amplified lipid A-induced IL-6, IL-8, and NF-κB activation.
  • This synergy was dependent on cholesterol-rich microdomains and mediated by caspase-8.

Conclusions:

  • Amphotericin B potentiates lipid A-induced inflammation via cholesterol-dependent pathways and caspase-8.
  • Periodontal treatment before amphotericin B may offer protection against this inflammatory response.

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