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.
We believe that wedge resection is a valid surgical intervention for SN type NTM; additional postoperative chemotherapy is unnecessary in cases with no residual lesions in the operated lung lobe.
The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have been found to frequently invade lymphatic vessels, and the prognosis of patients with lung adenocarcinoma with an MPP is poor. In the present study, the cancer cells of lung adenocarcinomas containing an MPP were found to express vimentin more extensively than those in lung adenocarcinoma without an MPP. The contribution of cancer cells in the MPP component to adenocarcinoma lymphatic invasion was assessed using vimentin as a marker. Vimentin expression was analyzed in the cancer cells present in each lymphatic vessel and compared with the expression of vimentin in the cancer cells in the adenocarcinomas without an MPP component. The results showed that the cancer cells in the lymphatic vessels expressed vimentin more extensively than those in the adenocarcinoma components without an MPP, suggesting that cancer cells derived from an MPP component are present in the lymphatic vessels. By contrast, the area of the MPP component in each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP components have a high capacity to invade lymphatic vessels and that their high invasive capacity may be associated with a poor prognosis in patients with adenocarcinoma with an MPP component.
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