Interleukin-10 stabilizes inhibitory kappaB-alpha in human monocytes - PubMed (original) (raw)

Affiliations

• PMID: 9872676

Interleukin-10 stabilizes inhibitory kappaB-alpha in human monocytes

B D Shames et al. Shock. 1998 Dec.

Abstract

Interleukin-10 (IL-10) protects animals from lethal endotoxemia. This beneficial effect is mediated, in part, by inhibition of inflammatory cytokine production, including tumor necrosis factor-alpha (TNF-alpha). Evidence suggests that IL-10 may inhibit activation of the transcription factor nuclear factor-kappaB (NF-kappaB) through an unknown mechanism. NF-kappaB activation in response to inflammatory signals is dependent upon degradation of its associated inhibitory peptide, inhibitory kappaB-alpha (IkappaB-alpha). We hypothesized that IL-10 prevents human monocyte NF-kappaB activation and resultant TNF-alpha production by stabilization of IkappaB-alpha. The purpose of this study was to determine the effect of IL-10 on lipopolysaccharide (LPS)-induced human monocyte TNF-alpha production, NF-kappaB activation, and IkappaB-alpha degradation. Monocytes were isolated from human donors. Cells were stimulated with endotoxin (LPS, 100 ng/mL) with and without human IL-10 (10 ng/mL). Following stimulation, TNF-alpha was measured in cell supernatants by ELISA, NF-kappaB activity by electrophoretic mobility shift assay, and IkappaB-alpha levels by Western blot. We observed that after LPS stimulation of human monocytes, TNF-alpha increased to 798+/-67 pg/mL (p < .001 versus control). IL-10 attenuated LPS-stimulated TNF-alpha production (297+/-54; p < .001 versus LPS alone). After LPS stimulation in human monocytes, IkappaB-alpha protein levels decreased, and NF-kappaB DNA binding increased. IL-10 pretreatment prevented LPS-induced decreases in IkappaB-alpha protein levels and attenuated NF-kappaB DNA binding. IL-10 appears to prevent activation of NF-kappaB by preserving IkappaB-alpha protein levels, leading to a reduction in TNF-alpha release.

PubMed Disclaimer

Similar articles

• LPS-Induced NF-kappaB activation and TNF-alpha release in human monocytes are protein tyrosine kinase dependent and protein kinase C independent.
  Shames BD, Selzman CH, Pulido EJ, Meng X, Meldrum DR, McIntyre RC Jr, Harken AH, Banerjee A. Shames BD, et al. J Surg Res. 1999 May 1;83(1):69-74. doi: 10.1006/jsre.1998.5564. J Surg Res. 1999. PMID: 10210645
• Effect of cross-tolerance between endotoxin and TNF-alpha or IL-1beta on cellular signaling and mediator production.
  Ferlito M, Romanenko OG, Ashton S, Squadrito F, Halushka PV, Cook JA. Ferlito M, et al. J Leukoc Biol. 2001 Nov;70(5):821-9. J Leukoc Biol. 2001. PMID: 11698503
• beta-Adrenergic agonists regulate NF-kappaB activation through multiple mechanisms.
  Ye RD. Ye RD. Am J Physiol Lung Cell Mol Physiol. 2000 Oct;279(4):L615-7. doi: 10.1152/ajplung.2000.279.4.L615. Am J Physiol Lung Cell Mol Physiol. 2000. PMID: 11000119 Review. No abstract available.
• The NFkappaBb/IkappaB system in acute inflammation.
  Lentsch AB, Ward PA. Lentsch AB, et al. Arch Immunol Ther Exp (Warsz). 2000;48(2):59-63. Arch Immunol Ther Exp (Warsz). 2000. PMID: 10807044 Review.

Cited by

• Deficiency of gammadelta T lymphocytes contributes to mortality and immunosuppression in sepsis.
  Chung CS, Watkins L, Funches A, Lomas-Neira J, Cioffi WG, Ayala A. Chung CS, et al. Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1338-43. doi: 10.1152/ajpregu.00283.2006. Epub 2006 Jun 22. Am J Physiol Regul Integr Comp Physiol. 2006. PMID: 16793935 Free PMC article.
• ABIN-3: a molecular basis for species divergence in interleukin-10-induced anti-inflammatory actions.
  Weaver BK, Bohn E, Judd BA, Gil MP, Schreiber RD. Weaver BK, et al. Mol Cell Biol. 2007 Jul;27(13):4603-16. doi: 10.1128/MCB.00223-07. Epub 2007 May 7. Mol Cell Biol. 2007. PMID: 17485448 Free PMC article.
• Interleukin-10 suppression of myeloid cell activation--a continuing puzzle.
  Williams LM, Ricchetti G, Sarma U, Smallie T, Foxwell BM. Williams LM, et al. Immunology. 2004 Nov;113(3):281-92. doi: 10.1111/j.1365-2567.2004.01988.x. Immunology. 2004. PMID: 15500614 Free PMC article. Review.
• The chemokine CCL2 is required for control of murine gastric Salmonella enterica infection.
  Depaolo RW, Lathan R, Rollins BJ, Karpus WJ. Depaolo RW, et al. Infect Immun. 2005 Oct;73(10):6514-22. doi: 10.1128/IAI.73.10.6514-6522.2005. Infect Immun. 2005. PMID: 16177325 Free PMC article.
• Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro.
  Schüller SS, Wisgrill L, Herndl E, Spittler A, Förster-Waldl E, Sadeghi K, Kramer BW, Berger A. Schüller SS, et al. Pediatr Res. 2017 Aug;82(2):215-225. doi: 10.1038/pr.2017.41. Epub 2017 May 24. Pediatr Res. 2017. PMID: 28288151

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.