Toll-like receptor 2, 3, 4, 5 ligands and interleukin-4 synergistically induce TARC production in nasal polyp fibroblasts.
OBJECTIVE
Although type 2 T helper (Th2) cytokines such as IL-4 and IL-5 play a crucial role in the pathogenesis of chronic sinusitis with allergy, the mechanism underlying the predominance of Th2 cytokines has yet to be clarified. Thymus and activation-regulated chemokine (TARC) has been known to facilitate the recruitment of Th2 polarized cells, resulting in high levels of Th2 cytokines in the sinus mucosa as well as nasal polyps. The nasal and sinus cavities are ideal sites for studying the interplay between microbial Toll-like receptor (TLR) ligands and chemokines. We investigated whether nasal polyp fibroblasts produce TARC when stimulated with the breakdown products of microorganisms (TLR ligands) and a Th2 cytokine (IL-4).


METHODS
Fibroblast lines were established from nasal polyp tissues. The expression of TARC mRNA was evaluated by real-time RT-PCR. The amount of TARC in the supernatants was measured by ELISA.


RESULTS
Combined stimulation with TLR 2, 3, 4, 5 ligands and IL-4 induced TARC gene expression and protein production in the cultured nasal polyp fibroblasts. This response was time-dependent.


CONCLUSIONS
These results suggest that nasal polyp fibroblasts contribute to innate immunity and may play an important role in the recruitment of Th2 cells into nasal polyps through the production of TARC.
Nonaka
Manabu
M
Department of Otorhinolaryngology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, Japan. nonaka@nms.ac.jp
Ogihara
Nozomu
N
Fukumoto
Akira
A
Sakanushi
Atsuko
A
Pawankar
Ruby
R
Yagi
Toshiaki
T
D000328:Adult; D001706:Biopsy; D002460:Cell Line; D054414:Chemokine CCL17 / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051194:Toll-Like Receptor 1 / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D051198:Toll-Like Receptor 5 / Q000502:physiology*
C106230:CCL17 protein, human; D054414:Chemokine CCL17; D012333:RNA, Messenger; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D015847:Interleukin-4