TY - JOUR
T1 - Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein
AU - Hung, Chih Hsing
AU - Chen, Li Chen
AU - Zhang, Zhongjian
AU - Chowdhury, Bhabadeb
AU - Lee, Wan Ling
AU - Plunkett, Beverly
AU - Chen, Chien Ho
AU - Myers, Allen C.
AU - Huang, Shau Ku
N1 - Funding Information:
This work was supported, in part, by National Institutes of Health (ROI-40274), Philip Morris USA Inc, National Science Council (Taiwan:NSC92-2314-B-182A-111), and Chang Gung Memorial Hospital, Taiwan (CMRP 1359).
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - BALF
KW - Bronchoalveolar lavage fluid
KW - CC10
KW - Clara cell
KW - OVA
KW - Ovalbumin
KW - Pulmonary Clara cell secretory 10-kd protein
KW - Recombinant pulmonary Clara cell secretory 10-kd protein
KW - T2
KW - asthma
KW - cytokine
KW - rCC10
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U2 - 10.1016/j.jaci.2004.05.042
DO - 10.1016/j.jaci.2004.05.042
M3 - Article
C2 - 15356574
AN - SCOPUS:4444233848
SN - 0091-6749
VL - 114
SP - 664
EP - 670
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -