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Establishment of an In vitro System to Study Intracellular Behavior of Candida glabrata in Human THP-1 Macrophages
13:47

Establishment of an In vitro System to Study Intracellular Behavior of Candida glabrata in Human THP-1 Macrophages

Published on: December 10, 2013

Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway

Katsuhiko Mizuno1, Tatsuki Fukami, Yasuyuki Toyoda

  • 1Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.

Life Sciences
|September 7, 2010
PubMed
Abstract

Insights

Terbinafine, an oral antifungal, triggers inflammatory responses by increasing pro-inflammatory cytokines like IL-8 and TNFα via the ERK1/2 pathway. This may explain terbinafine-induced liver injury.

Area of Science:

  • Immunology
  • Pharmacology
  • Toxicology

Background:

  • Oral antifungal terbinafine can cause liver injury with inflammatory responses.
  • The precise mechanism underlying terbinafine-induced liver injury remains unknown.
  • Investigating the pro-inflammatory cytokine release from human monocytic cells is crucial.

Purpose of the Study:

  • To examine the inflammatory reactions caused by terbinafine and other antifungal drugs.
  • To determine if terbinafine increases the release of pro-inflammatory cytokines.
  • To elucidate the underlying molecular pathways involved in terbinafine-induced inflammation.

Main Methods:

  • Measured mRNA expression and release of IL-8 and TNFα from THP-1 and HL-60 cells treated with antifungal drugs.
  • Investigated the effects of terbinafine on ERK1/2, p38 MAPK, and JNK1/2 phosphorylation.
  • Utilized MEK1/2 and p38 MAPK inhibitors to assess pathway involvement.

Main Results:

  • Terbinafine significantly increased IL-8 and TNFα release from THP-1 and HL-60 cells, unlike fluconazole.
  • Terbinafine treatment elevated ERK1/2 and p38 MAP kinase phosphorylation in THP-1 cells.
  • Inhibition of the ERK1/2 pathway, but not p38 MAPK, suppressed terbinafine-induced cytokine release.

Conclusions:

  • Terbinafine stimulates monocytes, leading to increased pro-inflammatory cytokine release.
  • The ERK1/2 pathway is critical for terbinafine-induced IL-8 and TNFα release.
  • This study suggests a mechanism for immune-mediated liver injury and an in vitro method for predicting adverse drug reactions.

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