title: Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein.
abstract: 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 T(H)2 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 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.
  
  
  CONCLUSIONS
  These results demonstrate, that CC10 plays a direct role in the regulation of T-cell-mediated inflammatory responses.
authors.affiliation: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224-6801, USA.
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Chen
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bhabadeb
authors.initials: B
authors.lastname: Chowdhury
authors.forename: Wan-Ling
authors.initials: WL
authors.lastname: Lee
authors.forename: Beverly
authors.initials: B
authors.lastname: Plunkett
authors.forename: Chien-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: Allen C
authors.initials: AC
authors.lastname: Myers
authors.forename: Shau-Ku
authors.initials: SK
authors.lastname: Huang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin