Poly(I:C) synergizes with Th2 cytokines to induce TARC/CCL17 in middle ear fibroblasts established from mucosa of otitis media with effusion.
CONCLUSIONS
These results suggest that middle ear fibroblasts contribute to the recruitment of Th2 cells into the middle ear by producing thymus and activation-regulated chemokine (TARC).


OBJECTIVE
Intractable otitis media is more common in atopic subjects and asthmatics than in the otherwise normal population. Although type 2 T helper (Th2) cytokines play crucial roles in the middle ear of these populations, the mechanism underlying the predominance of Th2 cytokines has yet to be clarified. TARC has been known to facilitate recruitment of Th2 polarized cells, resulting in high levels of Th2 cytokines in the middle ear. We investigated whether middle ear-derived fibroblasts produce TARC when stimulated with poly(I:C) and Th2 cytokines (IL-4, IL-13).


METHODS
Fibroblast lines were established from middle ear mucosa. TARC mRNA expression was evaluated by real-time RT-PCR. The amount of TARC in the culture supernatants was measured by ELISA.


RESULTS
Poly(I:C) induced only TARC gene expression in middle ear-derived fibroblasts. Combined stimulation with poly(I:C) and Th2 cytokine (IL-4, IL-13) synergistically induced TARC production by the cultured middle ear-derived fibroblasts. This response was dose and time dependent.
Nonaka
Manabu
M
Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan. nonaka@nms.ac.jp
Ogihara
Nozomu
N
Fukumoto
Akira
A
Sakanushi
Atsuko
A
Pawankar
Ruby
R
Yagi
Toshiaki
T
D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000235:genetics*; D004432:Ear, Middle / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D009092:Mucous Membrane / Q000166:cytology; D010034:Otitis Media with Effusion / Q000378:metabolism / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D007369:Interferon Inducers; D018793:Interleukin-13; D012333:RNA, Messenger; D015847:Interleukin-4; D011070:Poly I-C