Induction of TARC Production by Lipopolysaccharide and Interleukin-4 in Nasal Fibroblasts

Abstract

Background: Th2 cell infiltration is a characteristic feature of allergic chronic sinusitis. However, the mechanisms that cause the predominance of Th2 cells in this disease have yet to be clarified. The airway is often exposed to not only Th2 cytokines but also bacterial products such as lipopolysaccharides (LPS). A CC chemokine, TARC, is a potent chemoattractant for Th2 cells. The objectives of this study were twofold. First, we examined whether nasal polyp fibroblasts were able to produce TARC when costimulated with LPS and IL-4. Second, we investigated whether there was any heterogeneity in TARC production among fibroblasts derived from different airway sites. Methods: Fibroblast lines were established from human biopsy tissue. The amount of TARC in the supernatants was measured by ELISA. The expression of TARC mRNA was quantitated by real-time PCR. Results: Combined stimulation with LPS and IL-4 significantly induced TARC production by nasal polyp fibroblasts in a dose- and time-dependent manner. This induction occurred in normal nasal fibroblasts, but not in normal lung fibroblasts. Conclusions: Via TARC production, nasal fibroblasts may play an important role in the recruitment of Th2 cells into the sinus mucosa as well as nasal polyps. The heterogeneity in TARC production may reflect functional differences between upper and lower airway fibroblasts.

AlternariaInduces Production of Thymic Stromal Lymphopoietin in Nasal Fibroblasts Through Toll-like Receptor 2

“…7,11 The proinflammatory cytokines IL-1β and TNF-α induce TLSP production through the NF-κB signal transduction pathway from nasal fibroblasts. 7 TSLP is an important cytokine that polarizes CD4 + T cells to Th2 cytokine-producing cells and plays a role as a potent growth and survival factor for Th2 cells.…”

Combined Stimulation of Nasal Polyp Fibroblasts With Poly IC, Interleukin 4, and Tumor Necrosis Factor α Potently Induces Production of Thymus- and Activation-Regulated Chemokine

“…22 Investigations of TARC expression and the effects of neutralizing antibodies to TARC in vivo have revealed an important role for this chemokine in T H 2 cellmediated inflammation. 23 In addition to immune cells such as monocytes and dendritic cells, 9,24 tissue-resident cells such as epithelial cells and fibroblasts in the nasal mucosa, 25,26 epithelial cells in the lung, 27 fibroblasts but not epithelial cells in the cornea, 9 and epithelial cells and fibroblasts in the skin 10,28 produce TARC in response to cytokines and bacterial products such as lipopolysaccharide. Our data reinforce the notion that nasal fibroblasts could be a main source of TARC, particularly in the case of viral infections of the upper airway.…”

Combined Stimulation with Poly(I:C), TNF-α and Th2 Cytokines Induces TARC Production by Human Fibroblasts from the Nose, Bronchioles and Lungs

“…The Th2 cytokines (IL-4 and IL-13) released by accumulated Th2 cells induce the production of other chemokines such as eotaxin, leading to eosinophil infiltration. Although epithelial cells are thought to be the main source of TARC, fibroblasts were identified as another source of this chemokine [7]. …”

“…The heterogeneity of fibroblasts has been documented [7,9]. For instance, lipopolysaccharide, a TLR4 ligand, induced RANTES and GM-CSF [9] and synergized with IL-4 to induce TARC [7] in nasal, but not lung fibroblasts.…”

“…The heterogeneity of fibroblasts has been documented [7,9]. For instance, lipopolysaccharide, a TLR4 ligand, induced RANTES and GM-CSF [9] and synergized with IL-4 to induce TARC [7] in nasal, but not lung fibroblasts. Combined stimulation using TNF-α with Th2 cytokines (IL-4 and IL-13) markedly increased TARC expression in corneal and dermal fibroblasts but not in lung fibroblasts [10].…”