2007 Fiscal Year Final Research Report Summary
Elucidation of intracellular mechanisms of nasal fibroblast activations
| Project/Area Number |
17591804
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
NONAKA Manabu Nippon Medical School, Otolaryngology, Associate Professor (70271351)
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| Project Period (FY) |
2005 – 2007
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| Keywords | fibroblast / Rho / chemokine / TLR |
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| Research Abstract |
Nasal polyposis is characterized by marked oedema, eosinophil infiltrations, sparse extracellular matrix and proliferating blood vessels. We hypothesized that these characteristics may, in part, due to distinct role of nasal fibroblasts. We used microalley to look at intracellular cascades of nasal and lung fibroblasts stimulated by TGF-β, IL-4, TLR ligands.
TGF-β induced smooth muscle α-actin and pro-collagen type 1 synthesis in lung, but not nasal fibroblasts. By contrast, TGF-β induced VEGF synthesis in both nasal and lung fibroblasts. After stimulation with TGF-β, Smad2, 3, 4 were translocated from the cytoplasm to the nucleus in lung fibroblasts, whereas only Smad3 was translocated in nasal fibroblasts. And after stimulation with TGF-β, Rho (Ras homology) mRNA was upregulated in lung fibroblasts, but not in nasal fibroblasts.
TLR2, 3, 4, 5 induced nasal fibroblasts to produce RANTES. Moreover, TLR2, 3, 4, 5 and IL-4 synergistically induced MCP-4 and TARC. These results indicate that nasal fibroblasts contribute to innate immunity and eosinophilic inflammation. Microalley analyses indicated that NF-κ B and STAT6 were important transcription factors for those synergistic induction of MCP-4 and TARC
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