Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein
Hung, CH; Chen, LC; Zhang, Z; Chowdhury, B; Lee, WL; Plunkett, B; Chen, CH; Myers, AC; Huang, SK
| HERO ID | 1639191 |
|---|---|
| In Press | No |
| Year | 2004 |
| Title | Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein |
| Authors | Hung, CH; Chen, LC; Zhang, Z; Chowdhury, B; Lee, WL; Plunkett, B; Chen, CH; Myers, AC; Huang, SK |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 114 |
| Issue | 3 |
| Page Numbers | 664-670 |
| Abstract | <strong>BACKGROUND: </strong>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.<br /><br /><strong>OBJECTIVE: </strong>The role of CC10 in the regulation of T(H)2 cytokine expression was investigated.<br /><br /><strong>METHODS: </strong>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.<br /><br /><strong>RESULTS: </strong>In vitro, a significant, dose-dependent suppressive effect of CC10 was found on T(H)2 cytokine expression, but not IFN-gamma, in splenocytes of antigen-sensitized mice. A similar suppressive effect was also noted in polarized CD4(+) T(H)2 cells, but not in naive CD4(+) T cells. In contrast, CC10 was able to induce IFN-gamma expression in naive CD4(+) T cells, but not in polarized T(H)1 cells. Furthermore, the suppression of T(H)2 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 T(H)2 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 T(H)2 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.<br /><br /><strong>CONCLUSION: </strong>These results demonstrate, that CC10 plays a direct role in the regulation of T-cell-mediated inflammatory responses. |
| Doi | 10.1016/j.jaci.2004.05.042 |
| Pmid | 15356574 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |