| Autor: |
Lee J; Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan., Nakagiri T, Kamimura D, Harada M, Oto T, Susaki Y, Shintani Y, Inoue M, Miyoshi S, Morii E, Hirano T, Murakami M, Okumura M |
| Jazyk: |
angličtina |
| Zdroj: |
International immunology [Int Immunol] 2013 May; Vol. 25 (5), pp. 319-32. Date of Electronic Publication: 2013 Feb 07. |
| DOI: |
10.1093/intimm/dxs158 |
| Abstrakt: |
The IL-6 amplifier, a positive feedback loop for NFκB signaling, which was originally found to be activated by IL-17A and IL-6 stimulation in non-immune cells, is molecularly a simultaneous activator of NFκB and signal transducer and activator of transcription 3 (STAT3), functionally a local chemokine inducer and pathologically a machinery for inflammation development. It has been shown that IL-6 amplifier activation in epithelial cells contributes to rejection responses in a mouse chronic rejection model that develops a bronchiolitis obliterans (BO)-like disease. We investigated whether the IL-6 amplifier is activated in BO regions of a human lung graft after allogeneic transplantation. NFκB and STAT3 molecules were phosphorylated in the epithelial regions of bronchi that localized in the BO regions. Additionally, chemokine ligand 2 (CCL2), and CD4(+) T cells and macrophages increased in these regions. Furthermore, human lung epithelial cells expressed CCL2 after stimulation by IFNγ in the presence of IL-6 and epidermal growth factor via enhanced STAT3 signaling, which parallels behavior seen in the mouse model. Thus, our results suggest that the IL-6 amplifier in the epithelial cells of grafts is involved in chronic rejection after lung transplantation, suggesting that the amplifier may be a valuable therapeutic target to prevent chronic rejection after lung transplantation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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