Tags

Type your tag names separated by a space and hit enter

Thiol modulation inhibits the interleukin (IL)-1-mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B.
Eur J Immunol. 1997 Nov; 27(11):3015-21.EJ

Abstract

The interleukin-1 receptor type I (IL-1RI) is associated with other proteins thus forming a complex system by which IL-1 exerts its various signals. The initiating event is still uncertain, but activation of a recently described receptor-associated protein kinase is one of the earliest events detectable (Martin et al., Eur. J. Immunol. 1994. 24: 1566). IL-1 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation. We therefore investigated whether the activation of the IL-1RI-associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL-1-mediated NF-kappa B activation. A murine T cell line, EL4, was stimulated with IL-1 with and without pretreatment with different compounds known to influence the cellular redox status. Thiol modifying agents like diamide, menadione, pyrrolidine dithiocarbamate (PDTC), diethyl dithiocarbamate or phenylarsine oxide inhibited the IL-1-induced activation of the IL-1RI-associated protein kinase. N-Acetylcysteine, alpha,alpha'-dipyridyl, aminotriazole or nitrofurantoin did not show any effect. The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine. The described conditions which inhibited or prevented the activation of the IL-1RI-associated kinase similarly impaired the activation of NF-kappa B in EL4 cells. From these observations we conclude that free thiols in the IL-1RI complex are essential for the activation of the IL-1RI-associated protein kinase and that this process is mandatory for IL-1 signaling leading to NF-kappa B activation.

Authors+Show Affiliations

German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9394832

Citation

Tewes, F, et al. "Thiol Modulation Inhibits the Interleukin (IL)-1-mediated Activation of an IL-1 Receptor-associated Protein Kinase and NF-kappa B." European Journal of Immunology, vol. 27, no. 11, 1997, pp. 3015-21.
Tewes F, Böl GF, Brigelius-Flohé R. Thiol modulation inhibits the interleukin (IL)-1-mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B. Eur J Immunol. 1997;27(11):3015-21.
Tewes, F., Böl, G. F., & Brigelius-Flohé, R. (1997). Thiol modulation inhibits the interleukin (IL)-1-mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B. European Journal of Immunology, 27(11), 3015-21.
Tewes F, Böl GF, Brigelius-Flohé R. Thiol Modulation Inhibits the Interleukin (IL)-1-mediated Activation of an IL-1 Receptor-associated Protein Kinase and NF-kappa B. Eur J Immunol. 1997;27(11):3015-21. PubMed PMID: 9394832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thiol modulation inhibits the interleukin (IL)-1-mediated activation of an IL-1 receptor-associated protein kinase and NF-kappa B. AU - Tewes,F, AU - Böl,G F, AU - Brigelius-Flohé,R, PY - 1997/12/12/pubmed PY - 1997/12/12/medline PY - 1997/12/12/entrez SP - 3015 EP - 21 JF - European journal of immunology JO - Eur J Immunol VL - 27 IS - 11 N2 - The interleukin-1 receptor type I (IL-1RI) is associated with other proteins thus forming a complex system by which IL-1 exerts its various signals. The initiating event is still uncertain, but activation of a recently described receptor-associated protein kinase is one of the earliest events detectable (Martin et al., Eur. J. Immunol. 1994. 24: 1566). IL-1 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation. We therefore investigated whether the activation of the IL-1RI-associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL-1-mediated NF-kappa B activation. A murine T cell line, EL4, was stimulated with IL-1 with and without pretreatment with different compounds known to influence the cellular redox status. Thiol modifying agents like diamide, menadione, pyrrolidine dithiocarbamate (PDTC), diethyl dithiocarbamate or phenylarsine oxide inhibited the IL-1-induced activation of the IL-1RI-associated protein kinase. N-Acetylcysteine, alpha,alpha'-dipyridyl, aminotriazole or nitrofurantoin did not show any effect. The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine. The described conditions which inhibited or prevented the activation of the IL-1RI-associated kinase similarly impaired the activation of NF-kappa B in EL4 cells. From these observations we conclude that free thiols in the IL-1RI complex are essential for the activation of the IL-1RI-associated protein kinase and that this process is mandatory for IL-1 signaling leading to NF-kappa B activation. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/9394832/Thiol_modulation_inhibits_the_interleukin__IL__1_mediated_activation_of_an_IL_1_receptor_associated_protein_kinase_and_NF_kappa_B_ L2 - https://doi.org/10.1002/eji.1830271139 DB - PRIME DP - Unbound Medicine ER -