A fulvic acid-like substance participates in the pro-inflammatory effects of cigarette smoke and wood smoke particles.

We tested the postulate that 1) a fulvic acid (FA)-like substance is included in cigarette smoke and wood smoke particle (WSP) and 2) cell exposure to this substance results in a disruption of iron homeostasis associated with a deficiency of the metal and an inflammatory response. The fluorescence excitation-emission matrix spectra of the water-soluble components of cigarette smoke condensate and WSP (Cig-WS and Wood-WS) approximated those for the standard reference materials, Suwanee River and Nordic fulvic acids (SRFA and NFA). Fourier transform infrared (FT-IR) spectra for the FA fraction of cigarette smoke and WSP (Cig-FA and Wood-FA), SRFA and NFA also revealed significant similarities (O-H bond in alcohols, phenols or carboxylates, C=O in ketones, aldehydes and carboxylates, and a significant carboxylate content). After exposure to Cig-WS and Wood-WS and the FA standards, iron was imported by respiratory epithelial cells reflecting a functional iron deficiency. The release of pro-inflammatory mediators interleukin (IL)-8 and IL-6 by respiratory epithelial cells also increased following exposures to Cig-WS, Wood-WS, SRFA, and NFA. Co-exposure of the respiratory epithelial cells with iron decreased supernatant concentrations of the ILs relative to exposures to Cig-WS, Wood-WS, SRFA and NFA alone. It is concluded that 1) FA-like substance is included in cigarette smoke and WSP and 2) respiratory epithelial cell exposure to this substance results in a disruption of iron homeostasis associated with both a cell deficiency of the metal and inflammatory response.