Particulate matter initiates inflammatory cytokine release by activation of capsaicin and acid receptors in a human bronchial epithelial cell line

Toxicol Appl Pharmacol. 1999 Jan 1;154(1):106-15. doi: 10.1006/taap.1998.8567.


Recent experiments have shown that human bronchial epithelial cells (i.e., BEAS-2B) release pro-inflammatory cytokines (i.e., IL-6 and TNFalpha) in a receptor-mediated fashion in response to the neuropeptides, substance P (SP), calcitonin gene-related protein (CGRP), and the prototype botanical irritant capsaicin. In the present experiments, we examined the relevance of these receptors to particulate matter (PM)-associated cellular inflammation. BEAS-2B cells, exposed to residual oil fly ash particles (ROFA), responded with an immediate (<30 s) increase in intracellular calcium levels ([Ca2+]i), increases of key inflammatory cytokine transcripts (i.e., IL-6, IL-8, TNFalpha) within 2 h exposure, and subsequent release of IL-6 and IL-8 cytokine protein after 4 h exposure. Pretreatment of BEAS-2B cells with pharmacological antagonists selective for the SP or CGRP receptors reduced the ROFA-stimulated IL-6 cytokine production by approximately 25 and 50%, respectively. However, pretreatment of these cells with capsazepine (CPZ), an antagonist for capsaicin (i.e., vanilloid) receptors, inhibited the immediate increases in [Ca2+]i, diminished transcript (i.e., IL-6, IL-8, TNFalpha) levels and reduced IL-6 cytokine release to control levels. BEAS-2B cells exposed to ROFA in calcium-free media failed to demonstrate increases of [Ca2+]i and showed reduced levels of cytokine transcript (i.e., IL-6, IL-8, TNFalpha) and IL-6 release, suggesting that ROFA-stimulated cytokine formation was partially dependent on extracellular calcium sources. A final set of experiments compared the inflammatory properties of the soluble and acidic insoluble components of ROFA. BEAS-2B cells, exposed to ROFA or ROFA that had been filtered through a 0.2-micrometer pore filter, produced equivocal IL-6. BEAS-2B cells exposed to pH 5.0 media for 15 min released moderate amounts of IL-6, 4 h later. This cytokine release could be blocked by amiloride, a pH receptor antagonist, but not by CPZ. BEAS-2B cells, pretreated with amiloride before ROFA exposure, showed a partial (approximately 25%) reduction of IL-6. Together, these data indicate that the acidic, soluble components of ROFA initiate cytokine release in BEAS-2B cells through activation of both capsaicin- and pH-sensitive irritant receptors.

MeSH terms

  • Air Pollutants*
  • Amiloride / pharmacology
  • Bronchi / metabolism*
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Calcium / metabolism
  • Capsaicin / metabolism*
  • Carbon / pharmacology*
  • Cell Line
  • Coal Ash
  • Cytokines / metabolism*
  • Epithelium / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Neurokinin-1 Receptor Antagonists
  • Particulate Matter
  • Receptors, Calcitonin Gene-Related Peptide / physiology
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / physiology*
  • Receptors, Neurokinin-1 / physiology
  • Substance P / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism


  • Air Pollutants
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Coal Ash
  • Cytokines
  • Interleukin-6
  • Interleukin-8
  • Neurokinin-1 Receptor Antagonists
  • Particulate Matter
  • Receptors, Calcitonin Gene-Related Peptide
  • Receptors, Drug
  • Receptors, Neurokinin-1
  • Tumor Necrosis Factor-alpha
  • Substance P
  • Carbon
  • Amiloride
  • Calcitonin Gene-Related Peptide
  • Capsaicin
  • Calcium