Abstract
Aim of the study: Both nasal and bronchial epithelial cells have evolved sophisticated mechanisms involved in cellular response to bacterial infection. Recognition of pathogens by TLR receptors activate the NF-κB transcription factor, and lead to production of wide spectrum of cytokines (TNF-α, IL-1β, IL-6 and IL-8). Released by epithelium proinflammatory cytokines intensify migration of macrophages to damaged tissues and modulate their pro-inflammatory functions. Based on traditional use of G. squarrosa aerial parts we hypothesized that successful treatment of cold-related diseases may arise from modulation of the pro-inflammatory functions of respiratory epithelium and human monocytes/macrophages. The biological activity of G. squarrosa extract and grindelic acid were compared with clarithromycin and budesonide used as positive controls. Methods: The expression of surface receptors (TLR-4, IL-10) and expression of adhesive molecules (ICAM-1, VCAM-1, E-selectin) was analyzed with flow cytometry. The macrophage attachment to the epithelial cells was assessed fluorimetrically. The p65 NF-κB concentration and cytokine production was measured spectrophotometrically using enzyme-linked immunosorbent assay. Antibacterial activity was examined by the standard disc-diffusion method and serial dilution method according to CLSI guidelines. Results: G. squarrosa extract and grindelic acid had no antimicrobial effect. However, we noticed significant modulation of pro-inflammatory functions of LPS-stimulated nasal and bronchial epithelium. G. squarrosa extract treatment resulted in decrease of TLR-4 expression and p65 NF-κB concentration and inhibition of cytokines synthesis (IL-8, TNF-α, IL-1β and IL-6) in both cellular models. Additionally, G. squarrosa extract slightly modulated ICAM-1 expression affecting on attachment of macrophages to epithelium. Only G. squarrosa extract was able to stimulate the anti-inflammatory functions of macrophages by inducing TGF-β release and IL-10 receptor surface expression. Grindelic acid, identified as a dominant compound in the plant extract, modulated pro-inflammatory functions of epithelium and macrophages slightly. Conclusion: The obtained results support traditional use of Grindelia squarrosa preparations for a treatment cold-associated diseases symptoms. In our opinion, the observed biological effect of extract may be a consequence of synergistic effect of all compounds present in the extract.
Highlights
Common cold is one of the most common occurring acute illnesses in humans
We have evaluated influence of Grindelia squarrosa extract on proinflammatory functions of LPS-stimulated nasal and bronchial epithelial cells and macrophages
In order to confirm the presence of grindelic acid, we isolated this compound from the extract using ethyl acetate partition and column chromatography (Supplementary Figure S1)
Summary
Common cold is one of the most common occurring acute illnesses in humans. In a large-scale survey, 25% of all those questioned in the United Kingdom had suffered from 3 to 6 colds during the previous year and 73% reported having a common cold at least once during this period. The acute episode of a cold is starting with viral infection and may be accompanied by bacterial superinfection. The most common bacterial isolates from people with cold syndromes include Gram-positive strains, such as Streptococcus pneumoniae responsible for pharyngitis, bronchitis or pneumonia (Klugman and Feldman, 2001); Staphylococcus aureus responsible for pharyngitis and epiglottitis, Hemophilus influenzae, which occupy a similar microenvironment within the nasopharynx as Streptococcus pneumoniae (Erwin and Smith, 2007), and other opportunistic organisms as Escherichia coli (Mizgerd, 2008). Using antibiotics bring benefits only for the treatment of secondary bacterial infections. The valuable approach in the cold treatment may be strengthen immune system in order to prevent the uncontrolled progression of inflammation, and protection of the respiratory epithelium against excessive damage
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