Morphological alteration of cultured tracheobronchial epithelial cells is accompanied by the expression of chemokines, MCP-1 and CINC/gro, in rats.
Morphologically altered epithelial cells are generally observed in fibrotic lung conditions and have been reported to produce several cytokines. To examine the relationship between morphological changes of the tracheobronchial epithelial cells (TBECs) and their chemokine production, we investigated, (1) the mRNA expression and protein secretion of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil chemoattractant/gro (CINC/gro), (2) morphological changes by electron microscopy, and (3) cytokeratin (CK) expression, using a primary culture system of rat TBECs. The constitutive secretion of MCP-1 in the culture supernatant of TBECs increased in a time-dependent manner, whereas the CINC/gro secretion was not changed. These results were consistent with the chemokines' mRNA expression observed by in situ hybridization. The constitutive secretions of MCP-1 and CINC/gro were inhibited partially but significantly by dexamethasone. With the extension of the culture period, the morphology of the TBECs became flat and spindle in shape, similar to squamous metaplasia, as observed on electron microscopy, and with strong expression of CK 14. Sequential staining using immunocytochemistry and in situ hybridization revealed the coexpression of MCP-1 mRNA and CK 14. These data indicate a significant relationship between the morphological squamoid alteration and the constitutive expression of MCP-1 but not of CINC/gro. It is thought that the squamous metaplasia of TBECs may accompany the alteration of cytokine production and play an important role in chronic lung inflammation.
First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
T
T
Yamamoto
K
K
Iyonaga
M
M
Takeya
N
N
Saita
M
M
Suga
M
M
Ando
K
K
Takahashi
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D007633:Keratins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*
D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007633:Keratins; D003907:Dexamethasone