Expression of MCP-4 by TLR ligand-stimulated nasal polyp fibroblasts.
CONCLUSIONS
These results indicate that nasal polyp fibroblasts contribute to innate immunity and eosinophilic inflammation such as nasal polyposis.


OBJECTIVE
It is generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play an essential role in the pathogenesis of nasal polyposis. Nasal polyposis is characterized by chronic eosinophilic inflammation. The mechanisms that cause the predominance of eosinophilic infiltration in nasal polyposis have yet to be clarified. There is growing evidence that fibroblasts could be a major source of Th2 chemokines. Because the nasal and paranasal mucosae are the first respiratory tissues that environmental agents encounter, those tissues are exposed to injurious agents, including microorganisms and their breakdown products. We investigated whether nasal polyp fibroblasts produce a C-C chemokine, MCP-4, when stimulated with the breakdown products of microorganisms and a Th2 cytokine (interleukin (IL)-4).


METHODS
Fibroblast lines were established from nasal polyp tissues. The expression of MCP-4 mRNA was evaluated by real-time RT-PCR. The amount of MCP-4 in the supernatants was measured by ELISA.


RESULTS
TLR2, 3, 4 and 5 ligands, but not TLR7/8 or 9 ligands, induced small amounts of MCP-4. TLR2, 3, 4 and 5 ligands synergized with IL-4 to induce the production of MCP-4.
Nonaka
Manabu
M
Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan. nonaka@nms.ac.jp
Fukumoto
Akira
A
Ogihara
Nozomu
N
Pawankar
Ruby
R
Sakanushi
Atsuko
A
Yagi
Toshiaki
T
D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D009298:Nasal Polyps / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
C099677:CCL13 protein, human; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D015847:Interleukin-4