CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis

T. Inoue, S. Fujishima, E. Ikeda, O. Yoshie, N. Tsukamoto, S. Aiso, N. Aikawa, A. Kubo, K. Matsushima, K. Yamaguchi

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Abstract

Pulmonary fibrosis is caused by various known and unknown aetiologies, but the key pathogenic mechanisms are still ill-defined. Chemokines are a large family of chemotactic cytokines that play pivotal roles in various inflammatory diseases. In the present study, the roles of chemokines in a rat model of radiation pneumonitis/pulmonary fibrosis were examined. Accumulation of inflammatory cells and pneumonitis were observed on day 28, and diffuse alveolar wall thickening with extensive fibrosis was observed on day 56. In addition to the previously reported CCL2 (macrophage chemoattractant protein-1) induction, selective upregulation of CCL22 (macrophage-derived chemokine) and CCL17 (thymus and activation-regulated chemokine) were demonstrated for the first time in the irradiated lung tissues. Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages. On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients. Since these two chemokines play pivotal roles in various type-2 T-helper cell-dominant diseases, it was speculated that CCL22, and probably CCL17, are involved in the pathophysiology of radiation pneumonitis/pulmonary fibrosis and idiopathic pulmonary fibrosis through the recruitment of CC chemokine receptor 4-positive type-2 T-helper cells and alveolar macrophages.

Original languageEnglish
Pages (from-to)49-56
Number of pages8
JournalEuropean Respiratory Journal
Volume24
Issue number1
DOIs
Publication statusPublished - 2004 Jul 1

Keywords

  • Bronchoalveolar lavage
  • CC chemokine receptor 4
  • CCL17
  • CCL22
  • Idiopathic pulmonary fibrosis
  • Type-2 T-helper cell

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Inoue, T., Fujishima, S., Ikeda, E., Yoshie, O., Tsukamoto, N., Aiso, S., Aikawa, N., Kubo, A., Matsushima, K., & Yamaguchi, K. (2004). CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis. European Respiratory Journal, 24(1), 49-56. https://doi.org/10.1183/09031936.04.00110203