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

Am J Respir Crit Care Med. 2010 May 1;181(9):908-16. doi: 10.1164/rccm.200904-0597OC. Epub 2010 Jan 21.


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-1beta, tumor necrosis factor-alpha, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Airway Remodeling / physiology
  • Animals
  • Cells, Cultured
  • Chemokine CCL11 / analysis
  • Chitinase-3-Like Protein 1
  • Chronic Disease
  • Cytokines / pharmacology
  • Down-Regulation
  • Eosinophilia / physiopathology*
  • Gene Expression
  • Gene Transfer Techniques
  • Glycoproteins / analysis*
  • Humans
  • Immunohistochemistry
  • Lectins / analysis*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Respiratory Mucosa / cytology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhinitis / physiopathology*
  • Sinusitis / physiopathology*
  • Up-Regulation
  • Uteroglobin / genetics
  • Uteroglobin / physiology*


  • Adipokines
  • CHI3L1 protein, human
  • Chemokine CCL11
  • Chitinase-3-Like Protein 1
  • Cytokines
  • Glycoproteins
  • Lectins
  • SCGB1A1 protein, human
  • Scgb1a1 protein, mouse
  • Uteroglobin