Chemokine-like factor 1, a novel cytokine, contributes to airway damage, remodeling and pulmonary fibrosis.
BACKGROUND
Chemokine-like factor 1 (CKLF1) was recently identified as a novel cytokine. The full-length CKLF1 cDNA contains 530 bp encoding 99 amino acid residues with a CC motif similar to that of other CC family chemokines. Recombinant CKLF1 exhibits chemotactic activity on leucocytes and stimulates proliferation of murine skeletal muscle cells. We questioned whether CKLF1 could be involved in the pathogenesis of inflammation and proliferation in the lung. Therefore we used efficient in vivo gene delivery method to investigate the biological effect of CKLF1 in the murine lung.


METHODS
CKLF1-expressing plasmid, pCDI-CKLF1, was constructed and injected into the skeletal muscles followed by electroporation. Lung tissues were obtained at the end of week 1, 2, 3 and 4 respectively after injection. The pathological changes in the lungs were observed by light microscope.


RESULTS
A single intramuscular injection of CKLF1 plasmid DNA into BALB/c mice caused dramatic pathological changes in the lungs of treated mice. These changes included peribronchial leukocyte infiltration, epithelial shedding, collagen deposition, proliferation of bronchial smooth muscle cells and fibrosis of the lung.


CONCLUSIONS
The sustained morphological abnormalities of the bronchial and bronchiolar wall, the acute pneumonitis and interstitial pulmonary fibrosis induced by CKLF1 were similar to phenomena observed in chronic persistent asthma, acute respiratory distress syndrome and severe acute respiratory syndrome. These data suggest that CKLF1 may play an important role in the pathogenesis of these important diseases and the study also implies that gene electro-transfer in vivo could serve as a valuable approach for evaluating the function of a novel gene in animals.
Tan
Ya-xia
YX
Department of Respiratory Diseases, First Affiliated Hospital, Peking University, Beijing 100034, China.
Han
Wen-ling
WL
Chen
Ying-yu
YY
Ouyang
Neng-tai
NT
Tang
Yan
Y
Li
Feng
F
Ding
Pei-guo
PG
Ren
Xiao-lan
XL
Zeng
Guang-qiao
GQ
Ding
Jing
J
Zhu
Tong
T
Ma
Da-long
DL
Zhong
Nan-shan
NS
D000818:Animals; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002465:Cell Movement; D018925:Chemokines / Q000235:genetics / Q000502:physiology*; D018274:Electroporation; D006801:Humans; D008168:Lung / Q000473:pathology*; D062792:MARVEL Domain-Containing Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids; D011658:Pulmonary Fibrosis / Q000209:etiology*
C432676:CKLF protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins