Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein

Chih Hsing Hung, Li Chen Chen, Zhongjian Zhang, Bhabadeb Chowdhury, Wan Ling Lee, Beverly Plunkett, Chien Ho Chen, Allen C. Myers, Shau Ku Huang

研究成果: 雜誌貢獻文章同行評審

72 引文 斯高帕斯(Scopus)

摘要

Background Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T-cell responses remains unknown. Objective The role of CC10 in the regulation of TH2 cytokine expression was investigated. Methods The levels of cytokine and GATA-3 expression were determined by ELISA and RT-PCR, respectively. Bronchoalveolar lavage fluid cell counts were also determined by using a standard protocol. CC10 expression in vivo was determined by immunocytochemistry and Western blotting. Results In vitro, a significant, dose-dependent suppressive effect of CC10 was found on TH2 cytokine expression, but not IFN-γ, in splenocytes of antigen-sensitized mice. A similar suppressive effect was also noted in polarized CD4+ TH2 cells, but not in naive CD4+ T cells. In contrast, CC10 was able to induce IFN-γ expression in naive CD4+ T cells, but not in polarized TH1 cells. Furthermore, the suppression of TH2 cytokine expression was concomitant with reduction of a critical transcription factor, GATA-3. Of significance was the finding that although no significant change was found in the decay kinetics of TH2 cytokine transcripts, a significant decrease in mRNA stability of GATA-3 was seen in CC10-treated cells. In vivo, reconstitution of the CC10 gene in CC10-deficient mice resulted in significantly lower levels of TH2 cytokines, concomitant with a decrease in GATA-3 expression, after challenge with Ag compared with those seen in mock-transduced mice, which are associated with reduced levels of pulmonary eosinophilia. Conclusion These results demonstrate, that CC10 plays a direct role in the regulation of T-cell-mediated inflammatory responses.
原文英語
頁(從 - 到)664-670
頁數7
期刊Journal of Allergy and Clinical Immunology
114
發行號3
DOIs
出版狀態已發佈 - 9月 2004
對外發佈

ASJC Scopus subject areas

  • 免疫學和過敏
  • 免疫學

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