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J Clin Invest. Nov 15, 1997; 100(10): 2443–2448.
PMCID: PMC508444

In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13.


IL-10 and IL-13 have powerful antiinflammatory activities in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered IL-10 or IL-13 have recently been shown to suppress neutrophil recruitment and ensuing lung injury by greatly depressing pulmonary production of TNF alpha. Transcriptional control of the TNF alpha gene is regulated by the nuclear factor kappa B (NF-kappa B). Activation of NF-kappa B involves the degradation of its cytoplasmic inhibitor I kappa B alpha, allowing the nuclear translocation of NF-kappa B, with ensuing transcriptional activation. In this study, we sought to determine whether the protective effects of IL-10 and IL-13 in IgG immune complex-induced lung injury were mediated by inhibition of NF-kappa B activation. Electrophoretic mobility shift analysis of nuclear extracts from alveolar macrophages and whole lung tissues demonstrated that both IL-10 and IL-13 suppressed nuclear localization of NF-kappa B after in vivo deposition of IgG immune complexes. Western blot analysis indicated that these effects were due to preserved protein expression of I kappa B alpha in both alveolar macrophages and whole lungs. Northern blot analysis of lung mRNA showed that, in the presence of IgG immune complexes, IL-10 and IL-13 augmented I kappa B alpha mRNA expression. These findings suggest that in vivo, IL-10 and IL-13 may operate by suppressing NF-kappa B activation through preservation of I kappa B alpha.

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Selected References

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  • Johnson KJ, Ward PA. Acute immunologic pulmonary alveolitis. J Clin Invest. 1974 Aug;54(2):349–357. [PMC free article] [PubMed]
  • Warner RL, Paine R, 3rd, Christensen PJ, Marletta MA, Richards MK, Wilcoxen SE, Ward PA. Lung sources and cytokine requirements for in vivo expression of inducible nitric oxide synthase. Am J Respir Cell Mol Biol. 1995 Jun;12(6):649–661. [PubMed]
  • Warren JS, Yabroff KR, Remick DG, Kunkel SL, Chensue SW, Kunkel RG, Johnson KJ, Ward PA. Tumor necrosis factor participates in the pathogenesis of acute immune complex alveolitis in the rat. J Clin Invest. 1989 Dec;84(6):1873–1882. [PMC free article] [PubMed]
  • Warren JS. Intrapulmonary interleukin 1 mediates acute immune complex alveolitis in the rat. Biochem Biophys Res Commun. 1991 Mar 15;175(2):604–610. [PubMed]
  • Mulligan MS, Vaporciyan AA, Miyasaka M, Tamatani T, Ward PA. Tumor necrosis factor alpha regulates in vivo intrapulmonary expression of ICAM-1. Am J Pathol. 1993 Jun;142(6):1739–1749. [PMC free article] [PubMed]
  • Shanley TP, Foreback JL, Remick DG, Ulich TR, Kunkel SL, Ward PA. Regulatory effects of interleukin-6 in immunoglobulin G immune-complex-induced lung injury. Am J Pathol. 1997 Jul;151(1):193–203. [PMC free article] [PubMed]
  • Shanley TP, Schmal H, Friedl HP, Jones ML, Ward PA. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury. J Immunol. 1995 Apr 1;154(7):3454–3460. [PubMed]
  • Shanley TP, Peters JL, Jones ML, Chensue SW, Kunkel SL, Ward PA. Regulatory effects of endogenous interleukin-1 receptor antagonist protein in immunoglobulin G immune complex-induced lung injury. J Clin Invest. 1996 Feb 15;97(4):963–970. [PMC free article] [PubMed]
  • Mulligan MS, Jones ML, Vaporciyan AA, Howard MC, Ward PA. Protective effects of IL-4 and IL-10 against immune complex-induced lung injury. J Immunol. 1993 Nov 15;151(10):5666–5674. [PubMed]
  • Mulligan MS, Warner RL, Foreback JL, Shanley TP, Ward PA. Protective effects of IL-4, IL-10, IL-12, and IL-13 in IgG immune complex-induced lung injury: role of endogenous IL-12. J Immunol. 1997 Oct 1;159(7):3483–3489. [PubMed]
  • Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. [PubMed]
  • Wang P, Wu P, Siegel MI, Egan RW, Billah MM. Interleukin (IL)-10 inhibits nuclear factor kappa B (NF kappa B) activation in human monocytes. IL-10 and IL-4 suppress cytokine synthesis by different mechanisms. J Biol Chem. 1995 Apr 21;270(16):9558–9563. [PubMed]
  • Deryckere F, Gannon F. A one-hour minipreparation technique for extraction of DNA-binding proteins from animal tissues. Biotechniques. 1994 Mar;16(3):405–405. [PubMed]
  • Kilgore KS, Schmid E, Shanley TP, Flory CM, Maheswari V, Tramontini NL, Cohen H, Ward PA, Friedl HP, Warren JS. Sublytic concentrations of the membrane attack complex of complement induce endothelial interleukin-8 and monocyte chemoattractant protein-1 through nuclear factor-kappa B activation. Am J Pathol. 1997 Jun;150(6):2019–2031. [PMC free article] [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Chiao PJ, Miyamoto S, Verma IM. Autoregulation of I kappa B alpha activity. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):28–32. [PMC free article] [PubMed]
  • Mulligan MS, Wilson GP, Todd RF, Smith CW, Anderson DC, Varani J, Issekutz TB, Miyasaka M, Tamatani T, Myasaka M, et al. Role of beta 1, beta 2 integrins and ICAM-1 in lung injury after deposition of IgG and IgA immune complexes. J Immunol. 1993 Mar 15;150(6):2407–2417. [PubMed]
  • Henkel T, Machleidt T, Alkalay I, Krönke M, Ben-Neriah Y, Baeuerle PA. Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B. Nature. 1993 Sep 9;365(6442):182–185. [PubMed]
  • Baldwin AS., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683. [PubMed]
  • Collart MA, Baeuerle P, Vassalli P. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Mol Cell Biol. 1990 Apr;10(4):1498–1506. [PMC free article] [PubMed]
  • Thomassen MJ, Divis LT, Fisher CJ. Regulation of human alveolar macrophage inflammatory cytokine production by interleukin-10. Clin Immunol Immunopathol. 1996 Sep;80(3 Pt 1):321–324. [PubMed]
  • Armstrong L, Jordan N, Millar A. Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes. Thorax. 1996 Feb;51(2):143–149. [PMC free article] [PubMed]
  • Berkman N, John M, Roesems G, Jose P, Barnes PJ, Chung KF. Interleukin 13 inhibits macrophage inflammatory protein-1 alpha production from human alveolar macrophages and monocytes. Am J Respir Cell Mol Biol. 1996 Sep;15(3):382–389. [PubMed]
  • Yanagawa H, Sone S, Haku T, Mizuno K, Yano S, Ohmoto Y, Ogura T. Contrasting effect of interleukin-13 on interleukin-1 receptor antagonist and proinflammatory cytokine production by human alveolar macrophages. Am J Respir Cell Mol Biol. 1995 Jan;12(1):71–76. [PubMed]
  • Cassatella MA, Meda L, Gasperini S, Calzetti F, Bonora S. Interleukin 10 (IL-10) upregulates IL-1 receptor antagonist production from lipopolysaccharide-stimulated human polymorphonuclear leukocytes by delaying mRNA degradation. J Exp Med. 1994 May 1;179(5):1695–1699. [PMC free article] [PubMed]
  • Muzio M, Re F, Sironi M, Polentarutti N, Minty A, Caput D, Ferrara P, Mantovani A, Colotta F. Interleukin-13 induces the production of interleukin-1 receptor antagonist (IL-1ra) and the expression of the mRNA for the intracellular (keratinocyte) form of IL-1ra in human myelomonocytic cells. Blood. 1994 Apr 1;83(7):1738–1743. [PubMed]

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