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Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes.
J Immunol. 1994 Aug 15; 153(4):1818-24.JI

Abstract

Bacterial LPS stimulates human monocytes to secrete inflammatory cytokines, which are involved in several disease processes. However, the mechanism of LPS activation of cytokine expression and secretion is not completely understood. In this study, we investigated the signal transduction pathways involved in LPS-stimulated TNF-alpha and IL-1 beta secretion. TNF-alpha and IL-1 beta secretion were completely blocked by protein kinase C (PKC) and cyclic nucleotide-dependent protein kinase inhibitor, H-7, but were not affected by H-89, a specific cyclic nucleotide-dependent protein kinase inhibitor. In addition, LPS was found to induce activation of PKC, reaching maximal activity at 30 min and returning to unstimulated levels after 60 min. LPS stimulation only slightly increased intracellular levels of diacylglycerol, the natural activator of PKC, and pretreatment of monocytes with the diacylglycerol-kinase inhibitor, R59022, did not affect LPS-stimulated TNF-alpha secretion. LPS-induced PKC activation was found not to be affected by blocking of the LPS receptor, CD14, with mAb or by inhibition of protein tyrosine kinase with herbimycin A. However, these agents suppressed LPS-induced TNF-alpha secretion and TNF-alpha mRNA accumulation. The results suggest that TNF-alpha and IL-1 beta secretion after LPS stimulation of human monocytes requires the activation of protein tyrosine kinase and PKC, upstream to the activation of gene transcription. The activation of PKC by LPS is probably mediated by a diacylglycerol-independent pathway.

Authors+Show Affiliations

Department of Periodontology, Eastman Dental Center, Rochester, NY 14620.No 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

7519214

Citation

Shapira, L, et al. "Involvement of Protein Kinase C and Protein Tyrosine Kinase in Lipopolysaccharide-induced TNF-alpha and IL-1 Beta Production By Human Monocytes." Journal of Immunology (Baltimore, Md. : 1950), vol. 153, no. 4, 1994, pp. 1818-24.
Shapira L, Takashiba S, Champagne C, et al. Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes. J Immunol. 1994;153(4):1818-24.
Shapira, L., Takashiba, S., Champagne, C., Amar, S., & Van Dyke, T. E. (1994). Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes. Journal of Immunology (Baltimore, Md. : 1950), 153(4), 1818-24.
Shapira L, et al. Involvement of Protein Kinase C and Protein Tyrosine Kinase in Lipopolysaccharide-induced TNF-alpha and IL-1 Beta Production By Human Monocytes. J Immunol. 1994 Aug 15;153(4):1818-24. PubMed PMID: 7519214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes. AU - Shapira,L, AU - Takashiba,S, AU - Champagne,C, AU - Amar,S, AU - Van Dyke,T E, PY - 1994/8/15/pubmed PY - 1994/8/15/medline PY - 1994/8/15/entrez SP - 1818 EP - 24 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 153 IS - 4 N2 - Bacterial LPS stimulates human monocytes to secrete inflammatory cytokines, which are involved in several disease processes. However, the mechanism of LPS activation of cytokine expression and secretion is not completely understood. In this study, we investigated the signal transduction pathways involved in LPS-stimulated TNF-alpha and IL-1 beta secretion. TNF-alpha and IL-1 beta secretion were completely blocked by protein kinase C (PKC) and cyclic nucleotide-dependent protein kinase inhibitor, H-7, but were not affected by H-89, a specific cyclic nucleotide-dependent protein kinase inhibitor. In addition, LPS was found to induce activation of PKC, reaching maximal activity at 30 min and returning to unstimulated levels after 60 min. LPS stimulation only slightly increased intracellular levels of diacylglycerol, the natural activator of PKC, and pretreatment of monocytes with the diacylglycerol-kinase inhibitor, R59022, did not affect LPS-stimulated TNF-alpha secretion. LPS-induced PKC activation was found not to be affected by blocking of the LPS receptor, CD14, with mAb or by inhibition of protein tyrosine kinase with herbimycin A. However, these agents suppressed LPS-induced TNF-alpha secretion and TNF-alpha mRNA accumulation. The results suggest that TNF-alpha and IL-1 beta secretion after LPS stimulation of human monocytes requires the activation of protein tyrosine kinase and PKC, upstream to the activation of gene transcription. The activation of PKC by LPS is probably mediated by a diacylglycerol-independent pathway. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7519214/Involvement_of_protein_kinase_C_and_protein_tyrosine_kinase_in_lipopolysaccharide_induced_TNF_alpha_and_IL_1_beta_production_by_human_monocytes_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=7519214 DB - PRIME DP - Unbound Medicine ER -