Tags

Type your tag names separated by a space and hit enter

Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkappaB alpha phosphorylation and degradation.
Mol Cell Biol. 1998 Jan; 18(1):78-84.MC

Abstract

Many actions of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) on gene expression are mediated by the transcription factor NF-kappaB. Activation of NF-kappaB by TNF and IL-1 is initiated by the phosphorylation of the inhibitory subunit, IkappaB, which targets IkappaB for degradation and leads to the release of active NF-kappaB. The nonsteroidal anti-inflammatory drug sodium salicylate (NaSal) interferes with TNF-induced NF-kappaB activation by inhibiting phosphorylation and subsequent degradation of the IkappaB alpha protein. Recent evidence indicated that NaSal activates the p38 mitogen-activated protein kinase (MAPK), raising the possibility that inhibition of NF-kappaB activation by NaSal is mediated by p38 MAPK. We now show that inhibition of TNF-induced IkappaB alpha phosphorylation and degradation by NaSal is prevented by treatment of cells with SB203580, a highly specific p38 MAPK inhibitor. Both p38 activation and inhibition of TNF-induced IkappaB alpha degradation were seen after only 30 s to 1 min of NaSal treatment. Induction of p38 MAPK activation and inhibition of TNF-induced IkappaB alpha degradation were demonstrated with pharmacologically achievable doses of NaSal. These findings provide evidence for a role of NaSal-induced p38 MAPK activation in the inhibition of TNF signaling and suggest a possible role for the p38 MAPK in the anti-inflammatory actions of salicylates. In addition, these results implicate the p38 MAPK as a possible negative regulator of TNF signaling that leads to NF-kappaB activation.

Authors+Show Affiliations

Department of Microbiology, Skirball Institute for Biomolecular Medicine, NYU Medical Center, New York 10016, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9418855

Citation

Schwenger, P, et al. "Activation of P38 Mitogen-activated Protein Kinase By Sodium Salicylate Leads to Inhibition of Tumor Necrosis Factor-induced IkappaB Alpha Phosphorylation and Degradation." Molecular and Cellular Biology, vol. 18, no. 1, 1998, pp. 78-84.
Schwenger P, Alpert D, Skolnik EY, et al. Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkappaB alpha phosphorylation and degradation. Mol Cell Biol. 1998;18(1):78-84.
Schwenger, P., Alpert, D., Skolnik, E. Y., & Vilcek, J. (1998). Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkappaB alpha phosphorylation and degradation. Molecular and Cellular Biology, 18(1), 78-84.
Schwenger P, et al. Activation of P38 Mitogen-activated Protein Kinase By Sodium Salicylate Leads to Inhibition of Tumor Necrosis Factor-induced IkappaB Alpha Phosphorylation and Degradation. Mol Cell Biol. 1998;18(1):78-84. PubMed PMID: 9418855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkappaB alpha phosphorylation and degradation. AU - Schwenger,P, AU - Alpert,D, AU - Skolnik,E Y, AU - Vilcek,J, PY - 1998/1/7/pubmed PY - 1998/1/7/medline PY - 1998/1/7/entrez SP - 78 EP - 84 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 18 IS - 1 N2 - Many actions of the proinflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) on gene expression are mediated by the transcription factor NF-kappaB. Activation of NF-kappaB by TNF and IL-1 is initiated by the phosphorylation of the inhibitory subunit, IkappaB, which targets IkappaB for degradation and leads to the release of active NF-kappaB. The nonsteroidal anti-inflammatory drug sodium salicylate (NaSal) interferes with TNF-induced NF-kappaB activation by inhibiting phosphorylation and subsequent degradation of the IkappaB alpha protein. Recent evidence indicated that NaSal activates the p38 mitogen-activated protein kinase (MAPK), raising the possibility that inhibition of NF-kappaB activation by NaSal is mediated by p38 MAPK. We now show that inhibition of TNF-induced IkappaB alpha phosphorylation and degradation by NaSal is prevented by treatment of cells with SB203580, a highly specific p38 MAPK inhibitor. Both p38 activation and inhibition of TNF-induced IkappaB alpha degradation were seen after only 30 s to 1 min of NaSal treatment. Induction of p38 MAPK activation and inhibition of TNF-induced IkappaB alpha degradation were demonstrated with pharmacologically achievable doses of NaSal. These findings provide evidence for a role of NaSal-induced p38 MAPK activation in the inhibition of TNF signaling and suggest a possible role for the p38 MAPK in the anti-inflammatory actions of salicylates. In addition, these results implicate the p38 MAPK as a possible negative regulator of TNF signaling that leads to NF-kappaB activation. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/9418855/Activation_of_p38_mitogen_activated_protein_kinase_by_sodium_salicylate_leads_to_inhibition_of_tumor_necrosis_factor_induced_IkappaB_alpha_phosphorylation_and_degradation_ L2 - https://journals.asm.org/doi/10.1128/MCB.18.1.78?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -