IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation

Jihye Lee, Tomoyuki Nakagiri, Daisuke Kamimura, Masaya Harada, Takahiro Oto, Yoshiyuki Susaki, Yasushi Shintani, Masayoshi Inoue, Shinichiro Miyoshi, Eiichi Morii, Toshio Hirano, Masaaki Murakami, Meinoshin Okumura

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)319-332
Number of pages14
JournalInternational Immunology
Volume25
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Cytokines
  • IL-6
  • Inflammation
  • NFκB
  • STAT3
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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