Induction of TARC production by lipopolysaccharide and interleukin-4 in nasal fibroblasts.
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.
Fukumoto
Akira
A
Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan. fukuchan-a@nms.ac.jp
Nonaka
Manabu
M
Ogihara
Nozomu
N
Pawankar
Ruby
R
D054414:Chemokine CCL17 / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009297:Nasal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D009298:Nasal Polyps / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D008070:Lipopolysaccharides; D015847:Interleukin-4