Particulate Matter Initiates Inflammatory Cytokine Release by Activation of Capsaicin and Acid Receptors in a Human Bronchial Epithelial Cell Line

doi:10.1006/taap.1998.8567

Toxicology and Applied Pharmacology

Volume 154, Issue 1, 1 January 1999, Pages 106-115

https://doi.org/10.1006/taap.1998.8567 Get rights and content

Abstract

Recent experiments have shown that human bronchial epithelial cells (i.e., BEAS-2B) release pro-inflammatory cytokines (i.e., IL-6 and TNFα) 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, TNFα) 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 ∼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, TNFα) 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⁺]_iand showed reduced levels of cytokine transcript (i.e., IL-6, IL-8, TNFα) 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-μm 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 (∼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.

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^☆: P. J. BarnesM. M. GrunsteinA. R. LeffA. J. Woolcock

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Regular ArticleParticulate Matter Initiates Inflammatory Cytokine Release by Activation of Capsaicin and Acid Receptors in a Human Bronchial Epithelial Cell Line☆

Abstract

J. Allergy Clin. Immunol.

Toxicol. Appl. Pharmacol.

Eur. J. Pharmacol.

Trends Neurosci.

Toxicol. Appl. Pharmacol.

Fundam. Appl. Toxicol.

Toxicol. Lett.

Toxicol. Appl. Pharmacol.

Environ. Res.

Eur. J. Pharmacol.

Toxicology

Environ. Res.

Neuroscience

Toxicol. Lett.

Environ. Res.

Neurosci. Lett.

J. Biol. Chem.

Jpn. J. Pharmacol.

Toxicol. Appl. Pharmacol.

Biochim. Biophys. Acta

Toxicol. Appl. Pharmacol.

Biochem. Biophys. Res. Commun.

Gen. Pharmacol.

Pain

Hear. Res.

Neural control of human airways in health and disease

Am. Rev. Respir. Dis.

Neurogenic inflammation in airways

Int. Arch. Allergy Appl. Immunol.

Sensory neuropeptides

Asthma

Hydroxyl free radicals generated by vanadyl[IV] induce cell blebbing in mitotic human Chang liver cells

Biometals

Capsazepine: A competitive antagonist of the sensory neurone excitant capsaicin

Br. J. Pharmacol.

Sensory neuron-specific actions of capsaicin: Mechanisms and applications

Trends Pharmacol. Sci.

Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurones

J. Physiol.

Measurement of acidic aerosol species in eastern Europe: Implications for air pollution epidemiology

Environ. Health Perspect.

The capsaicin receptor: A heat-activated ion channel in the pain pathway

Nature

Airway hyperresponsiveness in guinea pigs exposed to acid-coated ultrafine particles

J. Toxicol. Environ. Health

Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37)

Am. J. Physiol.

Soluble transition metals mediate the acute pulmonary injury and airway hyperreactivity induced by residual oil fly ash particles

Chest

Soluble transition metals mediate residual oil fly ash induced acute lung injury

J. Toxicol. Environ. Health

Regular Article
Particulate Matter Initiates Inflammatory Cytokine Release by Activation of Capsaicin and Acid Receptors in a Human Bronchial Epithelial Cell Line☆