Combined stimulation with Poly(I:C), TNF-alpha and Th2 cytokines induces TARC production by human fibroblasts from the nose, bronchioles and lungs.
BACKGROUND
Th2 cells trigger allergic diseases in the respiratory tract. However, the mechanisms that cause Th2 cell infiltration remain unclear. Viral infections exacerbate allergic diseases in the respiratory tract. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. Resident fibroblasts are thought to contribute to inflammatory cell infiltration through chemokine production. We compared the abilities of nasal, bronchiolar and lung fibroblasts to produce TARC.


METHODS
Expression of TARC mRNA was evaluated by real-time RT-PCR, while the amount of TARC in supernatants was measured by ELISA.


RESULTS
Costimulation with TNF-alpha and Th2 cytokines (IL-4, IL-13) or with poly(I:C) and Th2 cytokines (IL-4, IL-13) induced TARC production by nasal (polyp and normal) fibroblasts. Costimulation with TNF-alpha and Th2 cytokines (IL-4, IL-13) also induced TARC production by both bronchiolar and lung fibroblasts, but costimulation with poly(I:C) and Th2 cytokines (IL-4, IL-13) caused no induction. Combined exposure of cells to poly(I:C), TNF-alpha and Th2 cytokines (IL-4, IL-13) resulted in substantial production of TARC by nasal and lung fibroblasts, but much less by bronchiolar fibroblasts.


CONCLUSIONS
TARC is directly inducible in diverse fibroblast populations from the respiratory tract (nose, bronchioles and lungs), but the mechanisms and levels of TARC production differ. Fibroblasts in the respiratory tract may contribute to Th2 cell infiltration and viral-induced exacerbation of allergic diseases, such as allergic sinusitis, asthma and allergic lung inflammation.
Nonaka
Manabu
M
Department of Otolaryngology, Nippon Medical School, Tokyo, Japan. nonaka@nms.ac.jp
Ogihara
Nozomu
N
Fukumoto
Akira
A
Sakanushi
Atsuko
A
Kusama
Kaoru
K
Pawankar
Ruby
R
Yagi
Toshiaki
T
D000328:Adult; D000368:Aged; D055745:Bronchioles / Q000166:cytology* / Q000276:immunology; D002478:Cells, Cultured; D054414:Chemokine CCL17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009666:Nose / Q000166:cytology* / Q000276:immunology; D009928:Organ Specificity; D011070:Poly I-C / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D054414:Chemokine CCL17; D014409:Tumor Necrosis Factor-alpha; D011070:Poly I-C