Tags

Type your tag names separated by a space and hit enter

Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK.
Mol Cell Biol. 1997 Nov; 17(11):6274-82.MC

Abstract

The adverse effects of lipopolysaccharide (LPS) are mediated primarily by tumor necrosis factor alpha (TNF-alpha). TNF-alpha production by LPS-stimulated macrophages is regulated at the levels of both transcription and translation. It has previously been shown that several mitogen-activated protein kinases (MAPKs) are activated in response to LPS. We set out to determine which MAPK signaling pathways are activated in our system and which MAPK pathways are required for TNF-alpha gene transcription or TNF-alpha mRNA translation. We confirm activation of the MAPK family members extracellular-signal-regulated kinases 1 and 2 (ERK1 and ERK2), p38, and Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), as well as activation of the immediate upstream MAPK activators MAPK/ERK kinases 1 and 4 (MEK1 and MEK4). We demonstrate that LPS also activates MEK2, MEK3, and MEK6. Furthermore, we demonstrate that dexamethasone, which inhibits the production of cytokines, including TNF-alpha, significantly inhibits LPS induction of JNK/SAPK activity but not that of p38, ERK1 and ERK2, or MEK3, MEK4, or MEK6. Dexamethasone also blocks the sorbitol but not anisomycin stimulation of JNK/SAPK activity. A kinase-defective mutant of SAPKbeta, SAPKbeta K-A, blocked translation of TNF-alpha, as determined by using a TNF-alpha translational reporting system. Finally, overexpression of wild-type SAPKbeta was able to overcome the dexamethasone-induced block of TNF-alpha translation. These data confirm that three MAPK family members and their upstream activators are stimulated by LPS and demonstrate that JNK/SAPK is required for LPS-induced translation of TNF-alpha mRNA. A novel mechanism by which dexamethasone inhibits translation of TNF-alpha is also revealed.

Authors+Show Affiliations

Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas 75235-9041, USA.No 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

9343388

Citation

Swantek, J L., et al. "Jun N-terminal Kinase/stress-activated Protein Kinase (JNK/SAPK) Is Required for Lipopolysaccharide Stimulation of Tumor Necrosis Factor Alpha (TNF-alpha) Translation: Glucocorticoids Inhibit TNF-alpha Translation By Blocking JNK/SAPK." Molecular and Cellular Biology, vol. 17, no. 11, 1997, pp. 6274-82.
Swantek JL, Cobb MH, Geppert TD. Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK. Mol Cell Biol. 1997;17(11):6274-82.
Swantek, J. L., Cobb, M. H., & Geppert, T. D. (1997). Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK. Molecular and Cellular Biology, 17(11), 6274-82.
Swantek JL, Cobb MH, Geppert TD. Jun N-terminal Kinase/stress-activated Protein Kinase (JNK/SAPK) Is Required for Lipopolysaccharide Stimulation of Tumor Necrosis Factor Alpha (TNF-alpha) Translation: Glucocorticoids Inhibit TNF-alpha Translation By Blocking JNK/SAPK. Mol Cell Biol. 1997;17(11):6274-82. PubMed PMID: 9343388.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK. AU - Swantek,J L, AU - Cobb,M H, AU - Geppert,T D, PY - 1997/10/29/pubmed PY - 1997/10/29/medline PY - 1997/10/29/entrez SP - 6274 EP - 82 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 17 IS - 11 N2 - The adverse effects of lipopolysaccharide (LPS) are mediated primarily by tumor necrosis factor alpha (TNF-alpha). TNF-alpha production by LPS-stimulated macrophages is regulated at the levels of both transcription and translation. It has previously been shown that several mitogen-activated protein kinases (MAPKs) are activated in response to LPS. We set out to determine which MAPK signaling pathways are activated in our system and which MAPK pathways are required for TNF-alpha gene transcription or TNF-alpha mRNA translation. We confirm activation of the MAPK family members extracellular-signal-regulated kinases 1 and 2 (ERK1 and ERK2), p38, and Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), as well as activation of the immediate upstream MAPK activators MAPK/ERK kinases 1 and 4 (MEK1 and MEK4). We demonstrate that LPS also activates MEK2, MEK3, and MEK6. Furthermore, we demonstrate that dexamethasone, which inhibits the production of cytokines, including TNF-alpha, significantly inhibits LPS induction of JNK/SAPK activity but not that of p38, ERK1 and ERK2, or MEK3, MEK4, or MEK6. Dexamethasone also blocks the sorbitol but not anisomycin stimulation of JNK/SAPK activity. A kinase-defective mutant of SAPKbeta, SAPKbeta K-A, blocked translation of TNF-alpha, as determined by using a TNF-alpha translational reporting system. Finally, overexpression of wild-type SAPKbeta was able to overcome the dexamethasone-induced block of TNF-alpha translation. These data confirm that three MAPK family members and their upstream activators are stimulated by LPS and demonstrate that JNK/SAPK is required for LPS-induced translation of TNF-alpha mRNA. A novel mechanism by which dexamethasone inhibits translation of TNF-alpha is also revealed. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/9343388/Jun_N_terminal_kinase/stress_activated_protein_kinase__JNK/SAPK__is_required_for_lipopolysaccharide_stimulation_of_tumor_necrosis_factor_alpha__TNF_alpha__translation:_glucocorticoids_inhibit_TNF_alpha_translation_by_blocking_JNK/SAPK_ L2 - https://journals.asm.org/doi/10.1128/MCB.17.11.6274?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -