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

Manabu Nonaka, MD; Nozomu Ogihara, MD; Akira Fukumoto, MD; Atsuko Sakanushi, MD; Ruby Pawankar, MD; Toshiaki Yagi, MD

Arch Otolaryngol Head Neck Surg. 2008;134(6):630-635.

Objective  To examine the effects of cytokines and poly IC on the expression of thymus- and activation-regulated chemokine (TARC), a potent chemoattractant for helper T-cell type 2 (T_H2) cells, in nasal polyp fibroblasts.

Design  Quantitative reverse transcription–polymerase chain reaction (RT-PCR) analysis.

Setting  Academic research.

Participants  Primary fibroblast lines were established from human nasal polyp biopsy tissue specimens (n = 5) removed at polypectomy.

Main Outcome Measures  The expression of TARC messenger RNA (mRNA) was evaluated by real-time RT-PCR. The amount of TARC in the supernatants was measured by enzyme-linked immunosorbent assay.

Results  Combined stimulation with interleukin 4 (IL-4) and tumor necrosis factor (TNF-) or with poly IC and IL-4 induced TARC production. Combined exposure of cells to poly IC, IL-4, and TNF- resulted in substantial amounts of TARC release into the culture medium. Quantitative RT-PCR analysis revealed that simultaneous stimulation with those 3 compounds induced a tremendous increase in the amount of TARC mRNA in the nasal polyp fibroblasts.

Conclusion  Nasal polyp fibroblasts contribute to T_H2 cell infiltration and RNA virus–induced exacerbation of T_H2-type airway inflammatory conditions such as allergic chronic sinusitis.

Author Affiliations: Department of Otolaryngology, Nippon Medical School, Tokyo, Japan.