Clara cell 10-kD protein suppresses chitinase 3-like 1 expression associated with eosinophilic chronic rhinosinusitis

Heng Wang, Xiao Bo Long, Ping Ping Cao, Nan Wang, Yang Liu, Yong Hua Cui, Shau Ku Huang, Zheng Liu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Rationale: Clara cell 10-kD (CC10) protein, an antiinflammatory molecule, is involved in inflammatory upper airway diseases, but its regulatory role is unclear, particularly in the process of chronic rhinosinusitis (CRS). Objectives: To investigate the regulatory mechanisms of CC10 in eosinophilic CRS (ECRS) using an allergic mouse model. Methods: Homozygous CC10-knockout mice were used to establish an allergic ECRS model. Phenotypic changes were examined by histology, cytokine ELISA, and gene microarray analysis. Differential expression of chitinase 3-like 1 (CHI3L1) was verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. The functional role of CHI3L1 in vivo was assessed by the use of anti-CHI3L1 antibody in ECRS mice. CHI3L1 gene expression regulated by inflammatory cytokines and CC10 protein was performed using BEAS-2B cell line. Measurements and Main Results: Compared with wild-type mice, a significantly greater extent of inflammatory cell infiltration and tissue remodeling was found in CC10-knockout ECRS mice, which was associated with significantly higher levels of various cytokines and eotaxin-1. CHI3L1 was up-regulated in ECRS mice with a significant further increase in CC10-knockout mice. Anti-CHI3L1 treatment markedly ameliorated eosinophilic inflammation. Furthermore, nasal mucosal CC10 gene transfer in CC10-knockout mice attenuated eosinophilic inflammation and suppressed the levels of CHI3L1. Moreover, significantly up-regulated expression of CHI3L1 was noted in human ECRS. IL-1β, tumor necrosis factor-α, and IL-13 were found to up-regulate CHI3L1 expression in BEAS-2B cells, whereas CC10 inhibited such up-regulation. Conclusions: These results suggest that CHI3L1 is a novel molecule involved in ECRS and that CC10 plays a regulatory role in ECRS, presumably by attenuating CHI3L1 expression.

Original languageEnglish
Pages (from-to)908-916
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume181
Issue number9
DOIs
Publication statusPublished - May 1 2010
Externally publishedYes

Fingerprint

Chitinases
Knockout Mice
Cytokines
Chitinase-3-Like Protein 1
Chemokine CCL11
Up-Regulation
Inflammation
Interleukin-13
Microarray Analysis
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-1
Nose
Genes
Histology
Proteins
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

Keywords

  • Inflammation
  • Mouse
  • Tissue remodeling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Clara cell 10-kD protein suppresses chitinase 3-like 1 expression associated with eosinophilic chronic rhinosinusitis. / Wang, Heng; Long, Xiao Bo; Cao, Ping Ping; Wang, Nan; Liu, Yang; Cui, Yong Hua; Huang, Shau Ku; Liu, Zheng.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 181, No. 9, 01.05.2010, p. 908-916.

Research output: Contribution to journalArticle

Wang, Heng ; Long, Xiao Bo ; Cao, Ping Ping ; Wang, Nan ; Liu, Yang ; Cui, Yong Hua ; Huang, Shau Ku ; Liu, Zheng. / Clara cell 10-kD protein suppresses chitinase 3-like 1 expression associated with eosinophilic chronic rhinosinusitis. In: American Journal of Respiratory and Critical Care Medicine. 2010 ; Vol. 181, No. 9. pp. 908-916.
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abstract = "Rationale: Clara cell 10-kD (CC10) protein, an antiinflammatory molecule, is involved in inflammatory upper airway diseases, but its regulatory role is unclear, particularly in the process of chronic rhinosinusitis (CRS). Objectives: To investigate the regulatory mechanisms of CC10 in eosinophilic CRS (ECRS) using an allergic mouse model. Methods: Homozygous CC10-knockout mice were used to establish an allergic ECRS model. Phenotypic changes were examined by histology, cytokine ELISA, and gene microarray analysis. Differential expression of chitinase 3-like 1 (CHI3L1) was verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. The functional role of CHI3L1 in vivo was assessed by the use of anti-CHI3L1 antibody in ECRS mice. CHI3L1 gene expression regulated by inflammatory cytokines and CC10 protein was performed using BEAS-2B cell line. Measurements and Main Results: Compared with wild-type mice, a significantly greater extent of inflammatory cell infiltration and tissue remodeling was found in CC10-knockout ECRS mice, which was associated with significantly higher levels of various cytokines and eotaxin-1. CHI3L1 was up-regulated in ECRS mice with a significant further increase in CC10-knockout mice. Anti-CHI3L1 treatment markedly ameliorated eosinophilic inflammation. Furthermore, nasal mucosal CC10 gene transfer in CC10-knockout mice attenuated eosinophilic inflammation and suppressed the levels of CHI3L1. Moreover, significantly up-regulated expression of CHI3L1 was noted in human ECRS. IL-1β, tumor necrosis factor-α, and IL-13 were found to up-regulate CHI3L1 expression in BEAS-2B cells, whereas CC10 inhibited such up-regulation. Conclusions: These results suggest that CHI3L1 is a novel molecule involved in ECRS and that CC10 plays a regulatory role in ECRS, presumably by attenuating CHI3L1 expression.",
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AU - Long, Xiao Bo

AU - Cao, Ping Ping

AU - Wang, Nan

AU - Liu, Yang

AU - Cui, Yong Hua

AU - Huang, Shau Ku

AU - Liu, Zheng

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N2 - Rationale: Clara cell 10-kD (CC10) protein, an antiinflammatory molecule, is involved in inflammatory upper airway diseases, but its regulatory role is unclear, particularly in the process of chronic rhinosinusitis (CRS). Objectives: To investigate the regulatory mechanisms of CC10 in eosinophilic CRS (ECRS) using an allergic mouse model. Methods: Homozygous CC10-knockout mice were used to establish an allergic ECRS model. Phenotypic changes were examined by histology, cytokine ELISA, and gene microarray analysis. Differential expression of chitinase 3-like 1 (CHI3L1) was verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. The functional role of CHI3L1 in vivo was assessed by the use of anti-CHI3L1 antibody in ECRS mice. CHI3L1 gene expression regulated by inflammatory cytokines and CC10 protein was performed using BEAS-2B cell line. Measurements and Main Results: Compared with wild-type mice, a significantly greater extent of inflammatory cell infiltration and tissue remodeling was found in CC10-knockout ECRS mice, which was associated with significantly higher levels of various cytokines and eotaxin-1. CHI3L1 was up-regulated in ECRS mice with a significant further increase in CC10-knockout mice. Anti-CHI3L1 treatment markedly ameliorated eosinophilic inflammation. Furthermore, nasal mucosal CC10 gene transfer in CC10-knockout mice attenuated eosinophilic inflammation and suppressed the levels of CHI3L1. Moreover, significantly up-regulated expression of CHI3L1 was noted in human ECRS. IL-1β, tumor necrosis factor-α, and IL-13 were found to up-regulate CHI3L1 expression in BEAS-2B cells, whereas CC10 inhibited such up-regulation. Conclusions: These results suggest that CHI3L1 is a novel molecule involved in ECRS and that CC10 plays a regulatory role in ECRS, presumably by attenuating CHI3L1 expression.

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