In vitro effect of glucocorticoids on nasal polyps

Abstract

Glucocorticoids are considered the main treatment option for nasal polyps, but their effect is only recently being understood. Aim To evaluate whether fluticasone propionate (FP) inhibits the inflammatory process induced by TNF-alpha in vitro , and to assess if NF-kappaB is associated to this inhibition. Study Design Experimental in vitro study. Materials and Methods Nasal polyp fibroblasts were cultured during 24 hours. Three different concentrations of FP (1, 10 and 100 nM, added to TNF-alpha) were compared to negative (without additive) and positive (TNF-alpha) controls. Gene expression (RTQ-PCR) and protein concentration (ELISA) of VCAM-1, ICAM-1, eotaxin and RANTES were measured, as well as the nuclear translocation of NF-kappaB. Results TNF-alpha significantly increased protein concentration and RNA expression of all the studied molecules, as well as the nuclear translocation of NF-kappaB, when compared to the negative control. FP decreased these parameters in a dose-dependent manner, statistically different from positive control up to 100nM. Conclusions FP extensively inhibited inflammatory recruiters, at both protein and RNA levels, confirming the ability of glucocorticoids to modulate the inflammatory process in nasal polyps. This inhibition was associated to decreased NF-kappaB nuclear translocation, demonstrating that this is an important mechanism of glucocorticoids action for nasal polyps.

Single Nucleotide Polymorphisms in TNF are Associated with Susceptibility to Aspirin-exacerbated Respiratory Disease but not to Cytokine Levels: a Study in Mexican Mestizo Population

“…This finding may be due to the therapeutic control being different between both patient groups, and as a consequence, the inflammation biomarkers are controlled in AERD; this result has been reported by Baraket et al, who demonstrated a decrease in TNF-α concentrations in a bronchioalveolar wash after treatment with inhaled fluticasone propionate in asthmatic patients [32]. Varela et al reported a similar finding in cultivating fibroblasts from nasal polyps, which, upon exposure to this steroid, inhibit the synthesis of cellular adhesion molecules [33]. In a similar model, Silvestri et al reported a decrease in the expression of ICAM-1, but not VCAM-1, in the presence of TNF-α [34].…”

Glucocorticoid Resistance in the Upper Respiratory Airways

“…The final effect of GC on nasal diseases is the inhibition of pro-inflammatory cytokines (IL-1 , TNF-, GM-CSF, IL-3, IL-5, IL-6), chemokines (IL-8, RANTES, eotaxin) and adhesion molecules (VCAM-1, ICAM-1) [1, 13,42]. Glucocorticoids also have a favorable effect on tissue remodeling (reducing MMP expression) [43,44], reduce mucin production [45], increase cell apoptosis [46,47], and decrease mast cell recruitment and activation [48].…”

Recognition of Candida albicans by gingival fibroblasts: The role of TLR2, TLR4/CD14, and MyD88

“…Similar to immune cells, studies have suggested that fibroblasts might utilize TLRs for sense pathogens, resulting in the production of many mediators contributing to the control of the infection [8,9]. Gingival fibroblasts constitutively express TLR2, TLR3, and TLR4 [10], and also the adhesion molecules ICAM-1 (CD54) and CD44 [11,12]. Activation of gingival fibroblast with microbial products induced the production of proinflammatory cytokines [13,14].…”