Thromb Haemost 2007; 97(03): 364-369
DOI: 10.1160/TH06-08-0473
Theme Issue Article
Schattauer GmbH

Resolution of inflammation: Intracellular feedback loops in the endothelium

Gabriele Winsauer
1   Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
,
Rainer de Martin
1   Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received 29 August 2006

Accepted after resubmission 24 January 2007

Publication Date:
28 November 2017 (online)

Summary

Timely termination of the inflammatory reaction is equally important as its elicitation, since a persistent or exaggerated response may lead to detrimental effects in the affected tissues and organs. Therefore, and in accordance with the complex and highly coordinated activation phase, negative regulatory mechanisms have evolved which function on multiple levels to ensure the appropriate termination of the inflammatory response. This review will focus on the mechanisms that are operative in endothelial cells to shut down the activity of specific signaling pathways and transcription factors that have been activated in response to pro-inflammatory mediators, and provide evidence that the stage for resolution is set already early in the activation phase of the inflammatory response. The elucidation of these feedback mechanisms is of importance for the understanding of acute versus chronic inflammation, and for novel strategies for therapeutic intervention.

 
  • References

  • 1 Mayno G. The healing hand: Man and wound in the ancient world. Cambridge, Massachusetts: Harvard University Press; 1975
  • 2 Ahmed A. et al. Induction of placental heme oxygenase- 1 is protective against TNFalpha-induced cytotoxicity and promotes vessel relaxation. Mol Med 2000; 6: 391-409.
  • 3 Nickoloff BJ. et al. Lessons learned from psoriatic plaques concerning mechanisms of tissue repair, remodeling, and inflammation. J Investig Dermatol Symp Proc 2006; 11: 16-29.
  • 4 Schreiber S. et al. Genetics of Crohn disease, an archetypal inflammatory barrier disease. Nat Rev Genet 2005; 6: 376-388.
  • 5 Weiner HL, Selkoe DJ. Inflammation and therapeutic vaccination in CNS diseases. Nature 2002; 420: 879-884.
  • 6 Yan SF. et al. Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond. Circ Res 2003; 93: 1159-1169.
  • 7 Henson PM. Dampening inflammation. Nat Immunol 2005; 6: 1177-1206.
  • 8 Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol 2005; 6: 1191-1197.
  • 9 Fiedler U. et al. Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation. Nat Med 2006; 12: 235-239.
  • 10 de Martin R. et al. The transcription factor NFkappa B and the regulation of vascular cell function. Arterioscler Thromb Vasc Biol 2000; 20: E83-88.
  • 11 Mayer H. et al. Deciphering regulatory patterns of inflammatory gene expression from interleukin- 1-stimulated human endothelial cells. Arterioscler Thromb Vasc Biol 2004; 24: 1192-1198.
  • 12 Zhao B. et al. Human endothelial cell response to gram-negative lipopolysaccharide assessed with cDNA microarrays. Am J Physiol Cell Physiol 2001; 281: C1587-1595.
  • 13 Chen ZJ. Ubiquitin signalling in the NF-kappaB pathway. Nat Cell Biol 2005; 7: 758-765.
  • 14 Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell 2002; 109: S81-96.
  • 15 Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 2004; 18: 2195-2224.
  • 16 Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005; 5: 749-759.
  • 17 Arenzana-Seisdedos F. et al. Inducible nuclear expression of newly synthesized I κ B α negatively regulates DNA-binding and transcriptional activities of NFkappa B. Mol Cell Biol 1995; 15: 2689-2696.
  • 18 Wrighton CJ. et al. Inhibition of endothelial cell activation by adenovirus-mediated expression of I kappa B alpha, an inhibitor of the transcription factor NFkappa B. J Exp Med 1996; 183: 1013-1022.
  • 19 Oitzinger W. et al. Adenovirus-mediated expression of a mutant IkappaB kinase 2 inhibits the response of endothelial cells to inflammatory stimuli. Blood 2001; 97: 1611-1617.
  • 20 Breuss JM. et al. Activation of nuclear factor-kappa B significantly contributes to lumen loss in a rabbit iliac artery balloon angioplasty model. Circulation 2002; 105: 633-638.
  • 21 Cejna M. et al. Inhibition of neointimal formation after stent placement with adenovirus-mediated gene transfer of I κ B α in the hypercholesterolemic rabbit model: initial results. Radiology 2002; 223: 702-708.
  • 22 Foxwell B. et al. Efficient adenoviral infection with I κ B α reveals that macrophage tumor necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent. Proc Natl Acad Sci USA 1998; 95: 8211-8215.
  • 23 Griesenbach U. et al. Anti-inflammatory gene therapy directed at the airway epithelium. Gene Ther 2000; 7: 306-313.
  • 24 Trescher K. et al. Inflammation and postinfarct remodeling: Overexpression of IkappaB prevents ventricular dilation via increasing TIMP levels. Cardiovasc Res 2006; 69: 746-754.
  • 25 Krikos A. et al. Transcriptional activation of the tumor necrosis factor alpha-inducible zinc finger protein, A20, is mediated by kappa B elements. J Biol Chem 1992; 267: 17971-17976.
  • 26 Cooper JT. et al. A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. J Biol Chem 1996; 271: 18068-18073.
  • 27 Wertz IE. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 2004; 430: 694-699.
  • 28 Mauro C. et al. ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappa B. J Biol Chem 2006; 281: 18482-18488.
  • 29 Bignell GR. et al. Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet 2000; 25: 160-165.
  • 30 Brummelkamp TR. et al. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature 2003; 424: 797-801.
  • 31 Kovalenko A. et al. The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature 2003; 424: 801-805.
  • 32 Trompouki E. et al. CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members. Nature 2003; 424: 793-796.
  • 33 Jono H. et al. NF-kappaB is essential for induction of CYLD, the negative regulator of NF-kappaB: evidence for a novel inducible autoregulatory feedback pathway. J Biol Chem 2004; 279: 36171-36174.
  • 34 Reiley W. et al. Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent phosphorylation. Mol Cell Biol 2005; 25: 3886-3895.
  • 35 Wu M. et al. SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription. J Biol Chem 2003; 278: 27072-27079.
  • 36 Huang J. et al. Identification of a novel serine/ threonine kinase that inhibits TNF-induced NF-kappaB activation and p53-induced transcription. Biochem Biophys Res Commun 2003; 309: 774-778.
  • 37 Rothwarf DM, Karin M. The NF-κB activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE; 1999. 1999 RE1
  • 38 Rossi A. et al. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature 2000; 403: 103-108.
  • 39 Quinlan KL. et al. Substance P activates coincident NF-AT- and NF-kappa B-dependent adhesion molecule gene expression in microvascular endothelial cells through intracellular calcium mobilization. J Immunol 1999; 163: 5656-5665.
  • 40 Hesser BA. et al. Down syndrome critical region protein 1 (DSCR1), a novel VEGF target gene that regulates expression of inflammatory markers on activated endothelial cells. Blood 2004; 104: 149-158.
  • 41 Mechtcheriakova D. et al. Specificity, diversity, and convergence in VEGF and TNF-alpha signaling events leading to tissue factor up-regulation via EGR-1 in endothelial cells. FASEB J 2001; 15: 230-242.
  • 42 Minami T. et al. Thrombin-induced auto-inhibitory factor, down syndrome critical region-1, attenuates NFAT-dependent vascular cell adhesion molecule-1 expression and inflammation in endothelium. J Biol Chem 2006; 281: 20503-20520.
  • 43 Carballo E. et al. Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science 1998; 281: 1001-1005.
  • 44 Carballo E. et al. Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability. Blood 2000; 95: 1891-1899.
  • 45 Chrestensen CA. et al. MAPKAP kinase 2 phosphorylates tristetraprolin on in vivo sites including Se178, a site required for 14–3–3 binding. J Biol Chem 2004; 279: 10176-10184.
  • 46 Lai WS. et al. Novel mRNA targets for tristetraprolin (TTP) identified by global analysis of stabilized transcripts in TTP-deficient fibroblasts. Mol Cell Biol. 2006 in press
  • 47 Carrick DM. et al. Genetic variations in ZFP36 and their possible relationship to autoimmune diseases. J Autoimmun 2006; 26: 182-196.
  • 48 Tchen CR. et al. The stability of tristetraprolin mRNA is regulated by mitogen activated protein kinase p38 and by tristetraprolin itself. J Biol Chem 2004; 7: 7
  • 49 Jing Q. et al. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell 2005; 120: 623-634.
  • 50 O'Neill LA. The role of MyD88-like adapters in Toll-like receptor signal transduction. Biochem Soc Trans 2003; 31: 643-647.
  • 51 Wesche H. et al. IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem 1999; 274: 19403-19410.
  • 52 Rao N. et al. A novel splice variant of interleukin-1 receptor (IL-1R)-associated kinase 1 plays a negative regulatory role in Toll/IL-1R-induced inflammatory signaling. Mol Cell Biol 2005; 25: 6521-6532.
  • 53 Janssens S. et al. Regulation of interleukin-1- and lipopolysaccharide-induced NF-κB activation by alternative splicing of MyD88. Curr Biol 2002; 12: 467-471.
  • 54 Kumar S. et al. Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. Biochem Biophys Res Commun 1997; 235: 474-478.
  • 55 Chen Y. et al. Severe pancreatitis with exocrine destruction and increased islet neogenesis in mice with suppressor of cytokine signaling-1 deficiency. Am J Pathol 2004; 165: 913-921.
  • 56 Mansell A. et al. Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat Immunol 2006; 7: 148-155.
  • 57 Saitoh T. et al. A20 is a negative regulator of IFN regulatory factor 3 signaling. J Immunol 2005; 174: 1507-1512.
  • 58 Gilchrist M. et al. Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 2006; 441: 173-178.
  • 59 Zhao Q. et al. The role of mitogen-activated protein kinase phosphatase-1 in the response of alveolar macrophages to lipopolysaccharide: attenuation of proinflammatory cytokine biosynthesis via feedback control of p38. J Biol Chem 2005; 280: 8101-8108.
  • 60 de Martin R. et al. Cytokine-inducible expression in endothelial cells of an I kappa B alpha-like gene is regulated by NF-κB. EMBO J 1993; 12: 2773-2779.
  • 61 Kiss-Toth E. et al. Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. J Biol Chem 2004; 279: 42703-42708.
  • 62 Charles CH. et al. Pip92: a short-lived, growth factorinducible protein in BALB/c 3T3 and PC12 cells. Mol Cell Biol 1990; 10: 6769-6774.
  • 63 Haider NB. et al. Evaluation and molecular characterization of EHD1, a candidate gene for Bardet- Biedl syndrome 1 (BBS1). Gene 1999; 240: 227-232.
  • 64 Miyashita T. et al. Osteoprotegerin (OPG) acts as an endogenous decoy receptor in tumour necrosis factorrelated apoptosis-inducing ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells. Clin Exp Immunol 2004; 137: 430-436.
  • 65 Tamai I. et al. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun 2000; 273: 251-260.
  • 66 Williams TM. et al. Identification of a zinc finger protein that inhibits IL-2 gene expression. Science 1991; 254: 1791-1794.
  • 67 Kumar D. et al. Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin- 1betaconverting enzyme-inhibitory protein. J Biol Chem 2000; 275: 2973-2978.
  • 68 Bamshad M. et al. Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome. Nat Genet 1997; 16: 311-315.
  • 69 Kuno K. et al. Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. J Biol Chem 1997; 272: 556-562.
  • 70 Tan KB. et al. Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells. Gene 1997; 204: 35-46.
  • 71 Lindsell CE. et al. Jagged: a mammalian ligand that activates Notch1. Cell 1995; 80: 909-917.