Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6.
Intestinal epithelial cells are a potentially important source for a number of cytokines that may modulate the immune response at the intestinal mucosa. We have recently begun to study the mechanisms that regulate IL-6 production by intestinal epithelial cells using the nontransformed crypt-like rat intestinal epithelial cell line IEC-6 as a model. Culture of the IEC-6 cells with human rIL-1 beta resulted in an enhanced secretion of IL-6 by the cells. RT-PCR analysis of IL-1 beta-treated cells showed an enhanced level of IL-6 mRNA at 4 h, suggesting that IL-1 beta enhanced IL-6 gene expression. In a previous study, transforming growth factor-beta (TGF-beta 1) was also found to enhance IL-6 secretion by the IEC-6 cells and because both IL-1 beta and TGF-beta may be present in inflamed mucosal tissue, the effect of adding both cytokines together was next investigated. Culture of the IEC-6 cells with both TGF-beta 1 and IL-1 beta resulted in a synergistic enhancement of IL-6 secretion that was seen even at high levels of both TGF-beta and IL-1 beta. IL-6 mRNA levels from cells treated with both TGF-beta 1 and IL-1 beta were also determined to be enhanced when compared to that of cells treated with IL-1 beta or TGF-beta 1 only, as determined by RT-PCR analysis. Pretreatment of the IEC-6 cells with TGF-beta 1 for 2 or 3 days before addition of the IL-1 beta induced the IEC-6 cells to differentiate and become more sensitive to stimulation by IL-1 beta. Subsequent experiments determined that TGF-beta enhanced the capacity of the IEC-6 cells to bind labeled IL-1 beta indicating that TGF-beta may have enhanced the expression of IL-1 receptors on the cells. These results suggest that the intestinal epithelial cell may represent an important source of IL-6 in inflammatory responses at the intestinal mucosa and that TGF-beta could potentiate this function.
McGee
D W
DW
Department of Microbiology, University of Alabama, Birmingham 35294.
Beagley
K W
KW
Aicher
W K
WK
McGhee
J R
JR
D000818:Animals; D002460:Cell Line; D004357:Drug Synergism; D004848:Epithelium / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta