Monocyte deactivation by interleukin 10 via inhibition of tyrosine kinase activity and the Ras signaling pathway - PubMed (original) (raw)

Monocyte deactivation by interleukin 10 via inhibition of tyrosine kinase activity and the Ras signaling pathway

Y Geng et al. Proc Natl Acad Sci U S A. 1994.

Abstract

Activation of monocytes by bacterial lipopolysaccharides (LPSs) is a central component in the pathogenesis of septic shock syndrome. Interleukin 10 (IL-10) is a potent monocyte-deactivating factor and transcriptionally inhibits LPS-induced expression of proinflammatory mediators. The intracellular signaling pathways of LPS have been only partially characterized and mechanisms of IL-10 signaling remain unknown. We show that LPS activates the protein tyrosine kinase (PTK) p56lyn and that this is associated with tyrosine phosphorylation of the protooncogene product Vav. These events are completely blocked by the tyrosine kinase inhibitor herbimycin A. LPS also increases Ras activation in monocytes. LPS-triggered phosphorylation of mitogen-activated protein kinase is a downstream activation event that is also reduced by herbimycin A. Analysis of the IL-10 effects shows that it completely inhibits the p56lyn tyrosine kinase activation and all other subsequent events in this pathway including Ras activation. The IL-10 effects are selective since it reduced PTK-dependent cytokine mRNA expression but not the PTK independent induction of c-jun and c-fos mRNA in LPS-activated monocytes. These results identify the Ras signaling pathway as a component of intracellular signaling in LPS-stimulated monocytes and define early events in this response as targets of monocyte deactivation by IL-10.

PubMed Disclaimer

Cited by

Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells.
Hubo M, Trinschek B, Kryczanowsky F, Tuettenberg A, Steinbrink K, Jonuleit H. Hubo M, et al. Front Immunol. 2013 Apr 3;4:82. doi: 10.3389/fimmu.2013.00082. eCollection 2013. Front Immunol. 2013. PMID: 23565116 Free PMC article.
Regulatory and signaling properties of the Vav family.
Bustelo XR. Bustelo XR. Mol Cell Biol. 2000 Mar;20(5):1461-77. doi: 10.1128/MCB.20.5.1461-1477.2000. Mol Cell Biol. 2000. PMID: 10669724 Free PMC article. Review. No abstract available.
Functional regions of the mouse interleukin-10 receptor cytoplasmic domain.
Ho AS, Wei SH, Mui AL, Miyajima A, Moore KW. Ho AS, et al. Mol Cell Biol. 1995 Sep;15(9):5043-53. doi: 10.1128/MCB.15.9.5043. Mol Cell Biol. 1995. PMID: 7544437 Free PMC article.
Expression of arthritis-causing HLA-B27 on Hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium.
Ikawa T, Ikeda M, Yamaguchi A, Tsai WC, Tamura N, Seta N, Trucksess M, Raybourne RB, Yu DT. Ikawa T, et al. J Clin Invest. 1998 Jan 1;101(1):263-72. doi: 10.1172/JCI471. J Clin Invest. 1998. PMID: 9421489 Free PMC article.
In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells.
Bissa M, Galli V, Schifanella L, Vaccari M, Rahman MA, Gorini G, Binello N, Sarkis S, Gutowska A, Silva de Castro I, Doster MN, Moles R, Ferrari G, Shen X, Tomaras GD, Montefiori DC, N'guessan KF, Paquin-Proulx D, Kozlowski PA, Venzon DJ, Choo-Wosoba H, Breed MW, Kramer J, Franchini G. Bissa M, et al. Vaccines (Basel). 2023 Oct 30;11(11):1662. doi: 10.3390/vaccines11111662. Vaccines (Basel). 2023. PMID: 38005994 Free PMC article.

References

1. Cell. 1992 Oct 16;71(2):335-42 - PubMed
1. J Immunol. 1993 Dec 15;151(12):6692-700 - PubMed
1. Nature. 1992 Dec 10;360(6404):600-3 - PubMed
1. Nature. 1985 Jun 20-26;315(6021):641-7 - PubMed
1. N Engl J Med. 1988 Mar 24;318(12):747-52 - PubMed

Monocyte deactivation by interleukin 10 via inhibition of tyrosine kinase activity and the Ras signaling pathway - PubMed (original) (raw)