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Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6.
J Immunol. 1993 Jul 15; 151(2):970-8.JI

Abstract

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.

Authors+Show Affiliations

Department of Microbiology, University of Alabama, Birmingham 35294.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8335922

Citation

McGee, D W., et al. "Transforming Growth Factor-beta and IL-1 Beta Act in Synergy to Enhance IL-6 Secretion By the Intestinal Epithelial Cell Line, IEC-6." Journal of Immunology (Baltimore, Md. : 1950), vol. 151, no. 2, 1993, pp. 970-8.
McGee DW, Beagley KW, Aicher WK, et al. Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6. J Immunol. 1993;151(2):970-8.
McGee, D. W., Beagley, K. W., Aicher, W. K., & McGhee, J. R. (1993). Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6. Journal of Immunology (Baltimore, Md. : 1950), 151(2), 970-8.
McGee DW, et al. Transforming Growth Factor-beta and IL-1 Beta Act in Synergy to Enhance IL-6 Secretion By the Intestinal Epithelial Cell Line, IEC-6. J Immunol. 1993 Jul 15;151(2):970-8. PubMed PMID: 8335922.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transforming growth factor-beta and IL-1 beta act in synergy to enhance IL-6 secretion by the intestinal epithelial cell line, IEC-6. AU - McGee,D W, AU - Beagley,K W, AU - Aicher,W K, AU - McGhee,J R, PY - 1993/7/15/pubmed PY - 1993/7/15/medline PY - 1993/7/15/entrez SP - 970 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 151 IS - 2 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8335922/Transforming_growth_factor_beta_and_IL_1_beta_act_in_synergy_to_enhance_IL_6_secretion_by_the_intestinal_epithelial_cell_line_IEC_6_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=8335922 DB - PRIME DP - Unbound Medicine ER -