The role of toll-like receptors in tributyltin-, dibutyltin-, and pentachlorophenol-induced stimulation of tumor necrosis factor-alpha (TNFα) production in human immune cells.

Authors

Latoya M Daniel, Aleshia Seaton-Terry, Ellie Bray, Meaghan Lewis, Zinia Hunter, Sophia Fisher, Brian Townsend, Margaret M Whalen

Published in

Archives of toxicology. Aug 25, 2026. Epub Aug 25, 2026.

Abstract

Tributyltin (TBT), Dibutyltin (DBT), and Pentachlorophenol (PCP) are persistent environmental contaminants that increase immune-cell production of pro-inflammatory cytokines and thus have the capacity to cause chronic inflammation and its associated pathologies such as cancer, cardiovascular disorders, and autoimmune conditions. TBT has been detected in human blood at concentrations up to 260 nM, DBT up to 0.3 µM, and PCP between 0.15 and 5 µM. Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine produced by immune cells in response to pathogen- or damage-associated molecular patterns (PAMPs/DAMPs) via Toll-like receptors (TLRs). Dysregulated TNF-α production contributes to chronic inflammatory pathology. Previous studies have shown that TBT, DBT, and PCP increase pro-inflammatory cytokine production by immune cells and that these increases depend on mitogen-activated protein kinases (MAPKs), which are downstream components of TLR activation. The current study indicates that TLR4 plays a role in TBT-, DBT-, and PCP-induced production of TNF-α. Additionally, TBT-induced TNF-α production was, at least in part, dependent on TLR2, DBT-induced TNF-α production on TLR1/2 and PCP-induced TNF-α production on TLR3 and TLR8. Blocking the initial component of TLR1/2, TLR2, TLR4, and TLR8 signaling, MyD88, led to very significant blockade of TBT- and PCP-induced TNF-α production. These findings provide additional understanding as to how compounds that are persistent pollutants activate production of a crucial regulator of inflammation, TNF-α, potentially contributing to chronic inflammation and its associated diseases.

PMID:
42637955
Bibliographic data and abstract were imported from PubMed on 25 Aug 2026.

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