Induction of eotaxin production by interleukin-4, interleukin-13 and lipopolysaccharide by nasal fibroblasts.
BACKGROUND
There is growing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. Fibroblasts are a major source of eotaxin. The severity of diseases with eosinophilic inflammation like nasal polyposis, atopic dermatitis and asthma, where Th2-type cytokines (IL-4 and IL-13) and TGF-beta are expressed locally, was shown to correlate with bacterial factors such as lipopolysaccharide (LPS) rather than allergen.


OBJECTIVE
We examined eotaxin production by nasal fibroblasts stimulated with IL-4 or IL-13 alone or in combination with LPS, and the effect of TGF-beta(1) on it. Moreover, we compared the magnitude of eotaxin produced by nasal fibroblasts with that produced by lung or skin fibroblasts.


METHODS
Fibroblast lines were established from human biopsy tissue. The expression of eotaxin mRNA was evaluated by RT-PCR. The amount of eotaxin in the supernatants was measured by ELISA.


RESULTS
IL-4, but not IL-13, synergized with LPS to produce eotaxin in a dose- and time-dependent manner. Sequential treatment of nasal fibroblasts with IL-4 and LPS did not have any effect. But when IL-4 and LPS were added together, synergy for eotaxin production was observed. Moreover, this synergy was observed in nasal and skin fibroblasts, but not in lung fibroblasts. The production of eotaxin by IL-4 and LPS was modulated by TGF-beta(1).


CONCLUSIONS
These results suggest that a co-stimulus like LPS is necessary for IL-4 to make a strong induction of eotaxin in eosinophilic inflammations such as nasal polyposis. Modulation by TGF-beta(1) may have important implications for the development of eosinophilic inflammation.
Nonaka
M
M
Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan. nonaka@nms.ac.jp
Pawankar
R
R
Fukumoto
A
A
Ogihara
N
N
Sakanushi
A
A
Yagi
T
T
D002460:Cell Line; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004802:Eosinophilia / Q000276:immunology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000276:immunology; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D018793:Interleukin-13; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4