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

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)664-670
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume114
Issue number3
DOIs
Publication statusPublished - Sep 2004
Externally publishedYes

Fingerprint

Cytokines
Lung
Proteins
T-Lymphocytes
Transcription Factor 3
Pulmonary Eosinophilia
RNA Stability
Bronchoalveolar Lavage Fluid
Anti-Inflammatory Agents
Cell Count
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Steroids
Antigens
Polymerase Chain Reaction
Genes

Keywords

  • asthma
  • BALF
  • Bronchoalveolar lavage fluid
  • CC10
  • Clara cell
  • cytokine
  • OVA
  • Ovalbumin
  • Pulmonary Clara cell secretory 10-kd protein
  • rCC10
  • Recombinant pulmonary Clara cell secretory 10-kd protein
  • T2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein. / Hung, Chih Hsing; Chen, Li Chen; Zhang, Zhongjian; Chowdhury, Bhabadeb; Lee, Wan Ling; Plunkett, Beverly; Chen, Chien Ho; Myers, Allen C.; Huang, Shau Ku.

In: Journal of Allergy and Clinical Immunology, Vol. 114, No. 3, 09.2004, p. 664-670.

Research output: Contribution to journalArticle

Hung, CH, Chen, LC, Zhang, Z, Chowdhury, B, Lee, WL, Plunkett, B, Chen, CH, Myers, AC & Huang, SK 2004, 'Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein', Journal of Allergy and Clinical Immunology, vol. 114, no. 3, pp. 664-670. https://doi.org/10.1016/j.jaci.2004.05.042
Hung, Chih Hsing ; Chen, Li Chen ; Zhang, Zhongjian ; Chowdhury, Bhabadeb ; Lee, Wan Ling ; Plunkett, Beverly ; Chen, Chien Ho ; Myers, Allen C. ; Huang, Shau Ku. / Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein. In: Journal of Allergy and Clinical Immunology. 2004 ; Vol. 114, No. 3. pp. 664-670.
@article{1ab88cb7db4c45a8947be0fe163cfe56,
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 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.",
keywords = "asthma, BALF, Bronchoalveolar lavage fluid, CC10, Clara cell, cytokine, OVA, Ovalbumin, Pulmonary Clara cell secretory 10-kd protein, rCC10, Recombinant pulmonary Clara cell secretory 10-kd protein, T2",
author = "Hung, {Chih Hsing} and Chen, {Li Chen} and Zhongjian Zhang and Bhabadeb Chowdhury and Lee, {Wan Ling} and Beverly Plunkett and Chen, {Chien Ho} and Myers, {Allen C.} and Huang, {Shau Ku}",
year = "2004",
month = "9",
doi = "10.1016/j.jaci.2004.05.042",
language = "English",
volume = "114",
pages = "664--670",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

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

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 - asthma

KW - BALF

KW - Bronchoalveolar lavage fluid

KW - CC10

KW - Clara cell

KW - cytokine

KW - OVA

KW - Ovalbumin

KW - Pulmonary Clara cell secretory 10-kd protein

KW - rCC10

KW - Recombinant pulmonary Clara cell secretory 10-kd protein

KW - T2

UR - http://www.scopus.com/inward/record.url?scp=4444233848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444233848&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2004.05.042

DO - 10.1016/j.jaci.2004.05.042

M3 - Article

VL - 114

SP - 664

EP - 670

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -