α1-antitrypsin activates protein phosphatase 2A to counter lung inflammatory responses

American Journal of Respiratory and Critical Care Medicine

Volumn 190, Issue 11, 2014, Pages 1229-1242

  Geraghty, Patrick ^a   Eden, Edward ^a   Pillai, Manju ^a   Campos, Michael ^b   McElvaney, Noel G ^c   Foronjy, Robert F ^a  

^a ST LUKE S ROOSEVELT HOSPITAL CENTER   (United States)

^b UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^c BEAUMONT HOSPITAL   (Ireland)

Author keywords

Cell signaling; Inflammation; Phosphorylation; PP2A; 1 antitrypsin

Indexed keywords

ALPHA 1 ANTITRYPSIN; ANTIINFLAMMATORY AGENT; PHOSPHOPROTEIN PHOSPHATASE 2; SERINE PROTEINASE INHIBITOR; TUMOR NECROSIS FACTOR ALPHA;

ADULT; ANIMAL; CHRONIC OBSTRUCTIVE LUNG DISEASE; DEFICIENCY; DISEASE MODEL; DRUG EFFECTS; FEMALE; HUMAN; IMMUNOLOGY; INFLAMMATION; LUNG; MALE; METABOLISM; MIDDLE AGED; MOUSE; NEUTROPHIL; PATHOPHYSIOLOGY; SMOKING;

ADULT; ALPHA 1-ANTITRYPSIN; ANIMALS; ANTI-INFLAMMATORY AGENTS; DISEASE MODELS, ANIMAL; FEMALE; HUMANS; INFLAMMATION; LUNG; MALE; MICE; MIDDLE AGED; NEUTROPHILS; PROTEIN PHOSPHATASE 2; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; SERINE PROTEINASE INHIBITORS; SMOKING; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84916235686     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201405-0872OC     Document Type: Article

References (46)

1. Hepper NG, Black LF, Gleich GJ, Kueppers F. The prevalence of alpha 1-antitrypsin deficiency in selected groups of patients with chronic obstructive lung disease. Mayo Clin Proc 1969;44:697-710.
2. Kalsheker NA. Molecular pathology of alpha 1-antitrypsin deficiency and its significance to clinical medicine. QJM 1994;87:653-658.
3. Ogushi F, Fells GA, Hubbard RC, Straus SD, Crystal RG. Z-type alpha 1-antitrypsin is less competent than M1-type alpha 1-antitrypsin as an inhibitor of neutrophil elastase. J Clin Invest 1987;80:1366-1374.
4. Hunt JM, Tuder R. Alpha 1 anti-trypsin: one protein, many functions. Curr Mol Med 2012;12:827-835.
5. Bergin DA, Hurley K, McElvaney NG, Reeves EP. Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent. Arch Immunol Ther Exp (Warsz) 2012;60:81-97.
6. Petrache I, Fijalkowska I, Medler TR, Skirball J, Cruz P, Zhen L, Petrache HI, Flotte TR, Tuder RM. alpha-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis. Am J Pathol 2006; 169:1155-1166.
7. Chan ED, Pott GB, Silkoff PE, Ralston AH, Bryan CL, Shapiro L. Alpha-1-antitrypsin inhibits nitric oxide production. J Leukoc Biol 2012;92: 1251-1260.
8. Shapiro L, Pott GB, Ralston AH. Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1. FASEB J 2001;15:115-122.
9. 1-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-α. Am J Respir Cell Mol Biol 2013;49: 143-150.
10. Carlson JA, Rogers BB, Sifers RN, Finegold MJ, Clift SM, DeMayo FJ, Bullock DW, Woo SL. Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice. J Clin Invest 1989;83: 1183-1190.
11. Carroll TP, Greene CM, O'Connor CA, Nolan AM, O'Neill SJ, McElvaney NG. Evidence for unfolded protein response activation in monocytes from individuals with alpha-1 antitrypsin deficiency. J Immunol 2010;184:4538-4546.
12. Bergin DA, Reeves EP, Meleady P, Henry M, McElvaney OJ, Carroll TP, Condron C, Chotirmall SH, Clynes M, O'Neill SJ, et al. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J Clin Invest 2010;120:4236-4250.
13. Geraghty P, Hardigan AA, Wallace AM, Mirochnitchenko O, Thankachen J, Arellanos L, Thompson V, D'Armiento JM, Foronjy RF. The glutathione peroxidase 1-protein tyrosine phosphatase 1B-protein phosphatase 2A axis: a key determinant of airway inflammation and alveolar destruction. Am J Respir Cell Mol Biol 2013;49:721-730.
14. Wallace AM, Hardigan A, Geraghty P, Salim S, Gaffney A, Thankachen J, Arellanos L, D'Armiento JM, Foronjy RF. Protein phosphatase 2A regulates innate immune and proteolytic responses to cigarette smoke exposure in the lung. Toxicol Sci 2012;126:589-599.
15. Chen J, Martin BL, Brautigan DL. Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation. Science 1992; 257:1261-1264.
16. Chen J, Parsons S, Brautigan DL. Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts. J Biol Chem 1994;269:7957-7962.
17. Churg A, Wang RD, Xie C, Wright JL. alpha-1-Antitrypsin ameliorates cigarette smoke-induced emphysema in the mouse. Am J Respir Crit Care Med 2003;168:199-207.
18. Chidwick K, Whichelow CE, Zhang Z, Fairburn K, Sachs JA, Blake DR, Winyard PG. Relationship between alpha 1-antitrypsin inactivation and tumor necrosis factor alpha concentration in the synovial fluid of patients with rheumatoid arthritis. Arthritis Rheum 1994;37:1723-1726.
19. Bergin DA, Reeves EP, Hurley K, Wolfe R, Jameel R, Fitzgerald S, McElvaney NG. The circulating proteinase inhibitor alpha-1 antitrypsin regulates neutrophil degranulation and autoimmunity. Science Translational Medicine 2014;6:217ra211.
20. Geraghty P, Eden E, Pillai M, Campos M, McElvaney N, Foronjy R. Alpha-1 antitrypsin counters inflammation by modulating the activity of protein phosphatase 2a [abstract]. Am J Respir Crit Care Med 2014;189:A4012.
21. Campos MA, Kueppers F, Stocks JM, Strange C, Chen J, Griffin R, Wang-Smith L, Brantly ML. Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: a multicenter, randomized, double-blind, crossover study (SPARK). COPD 2013;10:687-695.
22. Taggart CC, Greene CM, McElvaney NG, O'Neill S. Secretory leucoprotease inhibitor prevents lipopolysaccharide-induced IkappaBalpha degradation without affecting phosphorylation or ubiquitination. J Biol Chem 2002;277:33648-33653.
23. Stockley RA. Neutrophils and protease/antiprotease imbalance. Am J Respir Crit Care Med 1999;160:S49-S52.
24. Janoff A. Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis. Am Rev Respir Dis 1985;132:417-433.
25. Brantly M. Alpha1-antitrypsin: not just an antiprotease: extending the half-life of a natural anti-in flammatory molecule by conjugation with polyethylene glycol. Am J Respir Cell Mol Biol 2002;27:652-654.
26. Kobayashi Y, Mercado N, Barnes PJ, Ito K. Defects of protein phosphatase 2A causes corticosteroid insensitivity in severe asthma. PLoS ONE 2011;6:e27627.
27. Hubbard RC, Fells G, Gadek J, Pacholok S, Humes J, Crystal RG. Neutrophil accumulation in the lung in alpha 1-antitrypsin deficiency. Spontaneous release of leukotriene B4 by alveolar macrophages. J Clin Invest 1991;88:891-897.
28. Ma S, Lin YY, He J, Rouhani FN, Brantly M, Turino GM. Alpha-1 antitrypsin augmentation therapy and biomarkers of elastin degradation. COPD 2013;10:473-481.
29. Wewers MD, Crystal RG. Alpha-1 antitrypsin augmentation therapy. COPD 2013;10:64-67.
30. Miskolci V, Castro-Alcaraz S, Nguyen P, Vancura A, Davidson D, Vancurova I. Okadaic acid induces sustained activation of NFkappaB and degradation of the nuclear IkappaBalpha in human neutrophils. Arch Biochem Biophys 2003;417:44-52.
31. Lu DJ, Takai A, Leto TL, Grinstein S. Modulation of neutrophil activation by okadaic acid, a protein phosphatase inhibitor. Am J Physiol 1992;262:C39-C49.
32. Alvarado-Kristensson M, Andersson T. Protein phosphatase 2A regulates apoptosis in neutrophils by dephosphorylating both p38 MAPK and its substrate caspase 3. J Biol Chem 2005;280:6238-6244.
33. Qiu Q, Zheng Z, Chang L, Zhao YS, Tan C, Dandekar A, Zhang Z, Lin Z, Gui M, Li X, et al. Toll-like receptor-mediated IRE1α activation as a therapeutic target for infl ammatory arthritis. EMBO J 2013;32:2477-2490.
34. Stockley RA, Miravitlles M, Vogelmeier C; Alpha One International Registry (A.I.R.). Augmentation therapy for alpha-1 antitrypsin deficiency: towards a personalised approach. Orphanet J Rare Dis 2013;8:149.
35. Sandoval J, Escobar J, Pereda J, Sacilotto N, Rodriguez JL, Sabater L, Aparisi L, Franco L, López-Rodas G, Sastre J. Pentoxifylline prevents loss of PP2A phosphatase activity and recruitment of histone acetyltransferases to proinflammatory genes in acute pancreatitis. J Pharmacol Exp Ther 2009;331:609-617.
36. Jin Jung K, Hyun Kim D, Kyeong Lee E, Woo Song C, Pal Yu B, Young Chung H. Oxidative stress induces inactivation of protein phosphatase 2A, promoting proinflammatory NF-κB in aged rat kidney. Free Radic Biol Med 2013;61C:206-217.
37. Chung HY, Cha B, Kim H. Inhibition of serine-threonine protein phosphatases in monocyte chemoattractant protein-1 expression in Helicobacter pylori-stimulated gastric epithelial cells. Ann N Y Acad Sci 2007;1095:220-227.
38. Escobar J, Pereda J, Arduini A, Sandoval J, Sabater L, Aparisi L, Lopez-Rodas G, Sastre J. Protein phosphatases and chromatin modifying complexes in the inflammatory cascade in acute pancreatitis. World J Gastrointest Pharmacol Ther 2010;1:75-80.
39. Avdi NJ, Malcolm KC, Nick JA, Worthen GS. A role for protein phosphatase-2A in p38 mitogen-activated protein kinase-mediated regulation of the c-Jun NH(2)-terminal kinase pathway in human neutrophils. J Biol Chem 2002;277:40687-40696.
40. Miskolci V, Castro-Alcaraz S, Nguyen P, Vancura A, Davidson D, Vancurova I. Okadaic acid induces sustained activation of NFkappaB and degradation of the nuclear IkappaBalpha in human neutrophils. Arch Biochem Biophys 2003;417:44-52.
41. Churg A, Dai J, Tai H, Xie C, Wright JL. Tumor necrosis factor-alpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown. Am J Respir Crit Care Med 2002;166: 849-854.
42. Härmälä-Braskén AS, Mikhailov A, Söderström TS, Meinander A, Holmström TH, Damuni Z, Eriksson JE. Type-2A protein phosphatase activity is required to maintain death receptor responsiveness. Oncogene 2003;22:7677-7 686.
43. Ahn JH, McAvoy T, Rakhilin SV, Nishi A, Greengard P, Nairn AC. Protein kinase A activates protein phosphatase 2A by phosphorylation of the B56delta subunit. Proc Natl Acad Sci USA 2007;104:2979-2984.
44. Tao J, Malbon CC, Wang HY. Insulin stimulates tyrosine phosphorylation and inactivation of protein-tyrosine phosphatase 1B in vivo. J Biol Chem 2001;276:29520-29525.
45. Dadke S, Kusari A, Kusari J. Phosphorylation and activation of protein tyrosine phosphatase (PTP) 1B by insulin receptor. Mol Cell Biochem 2001;221:147-154.
46. Seino S, Shibasaki T. PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 2005;85:1303-1342.