Recent studies evaluated the impact of dust exposure on pure and mixed cultures of Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa, revealing increased biofilm formation and altered sensitivities to HO. In this study, we examined the impact of lead (Pb), house, road, and combined dust on K. pneumoniae and P. aeruginosa in pure, mixed, or eukaryotic co-culture with human alveolar basal epithelial (A549) cells. Although no impact on pure or mixed culture growth was observed when bacteria were exposed to Pb, house, or road dust, increased biofilm was produced by P. aeruginosa in the presence of 0.8 μg/mL of Pb, while P. aeruginosa and K. pneumoniae both exhibited increased biofilm production in the presence of 100 μg/mL of house, road, and combined dust. When co-cultured with eukaryotic A549 cells, both bacteria demonstrated increased proliferation 6 h post-infection when challenged with house, road, or combined dust. However, when mixed bacteria were co-cultured with A549 cells, P. aeruginosa exhibited a significant ~ 1.5-fold increased proliferation in the presence of 100 μg/mL house, road, or combined dust. In sharp contrast, K. pneumoniae exhibited significantly reduced proliferation, when in mixed (with P. aeruginosa) A-549 co-culture, following exposure to 100 μg/mL house, road, or combined dust. To evaluate whether a host cell inflammatory response contributed to this disparity, NF-κB activation was evaluated in each co-culture infection. K. pneumoniae-A-549 co-culture, treated with 100 μg/mL of combined dust, exhibited no alterations in NF-κB translocation to the nucleus. Further, no differences in cytokine production were observed in the K. pneumoniae A-549 co-culture treated with 100 μg/mL of house dust. Taken together, these data suggest that within the lung environment, mixed infections exposed to dust or dust contaminants could benefit one organism at the expense of the other, independent of the activation of inflammatory pathways.
Both natural and synthetic compounds that release hydrogen sulfide (H2S) such as diallyl trisulfide and naproxen‐H2S hybrids growth and proliferation of human colon HT29 cells (Lai et al. J. Cell. Mol. Med 19: 474, 2014; Kodela et al. Drug Des. Dev. Ther. 9:4873, 2015). Aims of the present study were: (a) to investigate the pharmacological action of L‐cysteine (substrate for the biosynthesis of H2S) and NaHS (H2S‐releasing compound) on proliferation of HT29 cells at different time‐points, and (b) to study the role of enzymes (cystathionine β‐synthase, CBS and cystathionine γ‐lyase, CSE) and K+‐ATP channels on the response elicited by H2S‐producing compounds in HT29 cells. The colon adenoma HT29 cells were treated with different concentrations of L‐cysteine (1 μM – 1 mM) and NaHS (1 μM – 1 mM) for 24 and 48 hours, in the absence and presence of inhibitors of CBS and CSE, amino‐oxyacetic acid (AOA, 1 mM), an inhibitor of K+‐ATP channels, glibenclamide (GLB, 10 μM). After incubation, the anti‐proliferative response on cells caused by various agents was determined by MTT Assay. At equimolar concentrations (10 μM and 1 mM), both L‐cysteine and NaHS caused concentration‐dependent inhibitions of cell proliferation after incubation for 24 h, but increased cell growth at these same concentrations after 48 h of incubation. For instance, at 10 μM, both L‐cysteine and NaHS increased cell proliferation by 37% and 51% after 48 h of incubation. Pretreatment of cells with AOA (1 mM) had no significant (P>0.05) effect on the inhibitory response caused by L‐cysteine and NaHS after 24 h incubation. Interestingly, AOA blocked and even reversed the increase in proliferation caused by L‐cysteine (10 μM and 1 mM) and NaHS (10 μM and 1 mM) after 48 h incubation. After 24 h, both L‐cysteine and NaHS caused additional inhibitory effects on cell proliferation in HT 29 cells pretreated with GLB (10 μM). GLB blocked and even reversed the increase in proliferation caused by L‐cysteine and NaHS in HT29 cells after 48 h incubation. We conclude that H2S‐releasing compounds can elicit a time‐dependent inhibitory or excitatory action on the proliferation of HT29 cells. The inhibitory/excitatory effects caused by these compounds depends, at least in part, on endogenous biosynthesis of new gas and the activity of K+‐ATP channels in HT29 cells. Support or Funding Information This research is supported by Tittle III under the Award Number P031B090216;Title III, Part B, Historically Black Graduate Institutions (HBGI) (CFDA No. 84.031B).
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