Interleukin-1beta stimulates the production of extracellular matrix in cultured human peritoneal mesothelial cells.
OBJECTIVE
To investigate the effect of interleukin-1beta (IL-1beta) on the production of extracellular matrix in cultured human peritoneal mesothelial cells (HPMCs).


METHODS
Cultured HPMCs were treated with or without IL-1beta. Cell morphology was observed. The expression of fibronectin, alpha1(I) procollagen, and transforming growth factor-beta1 (TGFbeta1) mRNAs was measured by Northern blot analysis. The cell surface expression of fibronectin and type I collagen was evaluated by immunofluorescent staining. Fibronectin and type I collagen in culture supernatant were measured by inhibition ELISA.


RESULTS
Interleukin-1beta induced morphologic change in HPMCs from a cuboidal epithelioid shape into an elongated fibroblastoid shape. The elongated cells were positive for cytokeratin although they had a fibroblastoid appearance. Treatment of HPMCs with IL-1beta resulted in increased expression of both fibronectin and alpha1(I) pro-collagen mRNA in dose- and time-dependent manners. Immunofluorescent staining showed strong and diffuse cytoplasmic expression of fibronectin and type I collagen in the cells treated with IL-1beta, whereas only weak perinuclear cytoplasmic staining was noted in the cells on media alone. The concentrations of secreted fibronectin and type I collagen in culture supernatant were significantly higher in the cells treated with IL-1beta than in the control cells. IL-1beta also stimulated the expression of TGFbeta1 mRNA. However, IL-1beta-induced fibronectin mRNA expression was only partially blocked by neutralizing anti-TGFbeta antibody.


CONCLUSIONS
Interleukin-1beta stimulated the production of extracellular matrix in cultured HPMCs along with the induction of morphologic changes. This may play a role in the development of peritoneal fibrosis caused by peritonitis or bioincompatible dialysate in continuous ambulatory peritoneal dialysis patients.
Yang
W S
WS
Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
Kim
B S
BS
Lee
S K
SK
Park
J S
JS
Kim
S B
SB
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007633:Keratins / Q000032:analysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000378:metabolism
D005353:Fibronectins; D007375:Interleukin-1; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007633:Keratins