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

The Journal of Allergy and Clinical Immunology
Chih-Hsing HungShau-Ku Huang

Abstract

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. The role of CC10 in the regulation of T(H)2 cytokine expression was investigated. 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. 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 s...Continue Reading

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