Tags

Type your tag names separated by a space and hit enter

TNF receptor-associated factor-2 is involved in both IL-1 beta and TNF-alpha signaling cascades leading to NF-kappa B activation and IL-8 expression in human intestinal epithelial cells.
J Immunol. 1999 Apr 15; 162(8):4447-54.JI

Abstract

Cytokine signaling involves the participation of many adaptor proteins, including the docking protein TNF receptor-associated factor-2 (TRAF-2), which is believed to transmit the TNF-alpha signal through both the I kappa B/NF-kappa B and c-Jun N-terminal kinase (JNK)/stress-related protein kinase (SAPK) pathways. The physiological role of TRAF proteins in cytokine signaling in intestinal epithelial cells (IEC) is unknown. We characterized the effect of a dominant-negative TRAF-2 delivered by an adenoviral vector (Ad5dnTRAF-2) on the cytokine signaling cascade in several IEC and also investigated whether inhibiting the TRAF-2-transmitting signal blocked TNF-alpha-induced NF-kappa B and IL-8 gene expression. A high efficacy and level of Ad5dnTRAF-2 gene transfer were obtained in IEC using a multiplicity of infection of 50. Ad5dnTRAF-2 expression prevented TNF-alpha-induced, but not IL-1 beta-induced, I kappa B alpha degradation and NF-kappa B activation in NIH-3T3 and IEC-6 cells. TNF-alpha-induced JNK activation was also inhibited in Ad5dnTRAF-2-infected HT-29 cells. Induction of IL-8 gene expression by TNF-alpha was partially inhibited in Ad5dnTRAF-2-transfected HT-29, but not in control Ad5LacZ-infected, cells. Surprisingly, IL-1 beta-mediated IL-8 gene expression was also inhibited in HT-29 cells as measured by Northern blot and ELISA. We concluded that TRAF-2 is partially involved in TNF-alpha-mediated signaling through I kappa B/NF-kappa B in IEC. In addition, our data suggest that TRAF-2 is involved in IL-1 beta signaling in HT-29 cells. Manipulation of cytokine signaling pathways represents a new approach for inhibiting proinflammatory gene expression in IEC.

Authors+Show Affiliations

Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill 27599, USA. job@med.unc.eduNo affiliation info availableNo affiliation info availableNo 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

10201981

Citation

Jobin, C, et al. "TNF Receptor-associated Factor-2 Is Involved in Both IL-1 Beta and TNF-alpha Signaling Cascades Leading to NF-kappa B Activation and IL-8 Expression in Human Intestinal Epithelial Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 162, no. 8, 1999, pp. 4447-54.
Jobin C, Holt L, Bradham CA, et al. TNF receptor-associated factor-2 is involved in both IL-1 beta and TNF-alpha signaling cascades leading to NF-kappa B activation and IL-8 expression in human intestinal epithelial cells. J Immunol. 1999;162(8):4447-54.
Jobin, C., Holt, L., Bradham, C. A., Streetz, K., Brenner, D. A., & Sartor, R. B. (1999). TNF receptor-associated factor-2 is involved in both IL-1 beta and TNF-alpha signaling cascades leading to NF-kappa B activation and IL-8 expression in human intestinal epithelial cells. Journal of Immunology (Baltimore, Md. : 1950), 162(8), 4447-54.
Jobin C, et al. TNF Receptor-associated Factor-2 Is Involved in Both IL-1 Beta and TNF-alpha Signaling Cascades Leading to NF-kappa B Activation and IL-8 Expression in Human Intestinal Epithelial Cells. J Immunol. 1999 Apr 15;162(8):4447-54. PubMed PMID: 10201981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF receptor-associated factor-2 is involved in both IL-1 beta and TNF-alpha signaling cascades leading to NF-kappa B activation and IL-8 expression in human intestinal epithelial cells. AU - Jobin,C, AU - Holt,L, AU - Bradham,C A, AU - Streetz,K, AU - Brenner,D A, AU - Sartor,R B, PY - 1999/4/14/pubmed PY - 1999/4/14/medline PY - 1999/4/14/entrez SP - 4447 EP - 54 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 162 IS - 8 N2 - Cytokine signaling involves the participation of many adaptor proteins, including the docking protein TNF receptor-associated factor-2 (TRAF-2), which is believed to transmit the TNF-alpha signal through both the I kappa B/NF-kappa B and c-Jun N-terminal kinase (JNK)/stress-related protein kinase (SAPK) pathways. The physiological role of TRAF proteins in cytokine signaling in intestinal epithelial cells (IEC) is unknown. We characterized the effect of a dominant-negative TRAF-2 delivered by an adenoviral vector (Ad5dnTRAF-2) on the cytokine signaling cascade in several IEC and also investigated whether inhibiting the TRAF-2-transmitting signal blocked TNF-alpha-induced NF-kappa B and IL-8 gene expression. A high efficacy and level of Ad5dnTRAF-2 gene transfer were obtained in IEC using a multiplicity of infection of 50. Ad5dnTRAF-2 expression prevented TNF-alpha-induced, but not IL-1 beta-induced, I kappa B alpha degradation and NF-kappa B activation in NIH-3T3 and IEC-6 cells. TNF-alpha-induced JNK activation was also inhibited in Ad5dnTRAF-2-infected HT-29 cells. Induction of IL-8 gene expression by TNF-alpha was partially inhibited in Ad5dnTRAF-2-transfected HT-29, but not in control Ad5LacZ-infected, cells. Surprisingly, IL-1 beta-mediated IL-8 gene expression was also inhibited in HT-29 cells as measured by Northern blot and ELISA. We concluded that TRAF-2 is partially involved in TNF-alpha-mediated signaling through I kappa B/NF-kappa B in IEC. In addition, our data suggest that TRAF-2 is involved in IL-1 beta signaling in HT-29 cells. Manipulation of cytokine signaling pathways represents a new approach for inhibiting proinflammatory gene expression in IEC. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10201981/TNF_receptor_associated_factor_2_is_involved_in_both_IL_1_beta_and_TNF_alpha_signaling_cascades_leading_to_NF_kappa_B_activation_and_IL_8_expression_in_human_intestinal_epithelial_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10201981 DB - PRIME DP - Unbound Medicine ER -