title: IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation.
abstract: 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.
authors: Laboratory of Developmental Immunology, JST-CREST, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
authors: Jihye
authors: J
authors: Lee
authors: Tomoyuki
authors: T
authors: Nakagiri
authors: Daisuke
authors: D
authors: Kamimura
authors: Masaya
authors: M
authors: Harada
authors: Takahiro
authors: T
authors: Oto
authors: Yoshiyuki
authors: Y
authors: Susaki
authors: Yasushi
authors: Y
authors: Shintani
authors: Masayoshi
authors: M
authors: Inoue
authors: Shinichiro
authors: S
authors: Miyoshi
authors: Eiichi
authors: E
authors: Morii
authors: Toshio
authors: T
authors: Hirano
authors: Masaaki
authors: M
authors: Murakami
authors: Meinoshin
authors: M
authors: Okumura
mesh_terms: D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001989:Bronchiolitis Obliterans / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016040:Lung Transplantation; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D015850:Interleukin-6