Impairment of lysosomal functions by azithromycin and chloroquine contributes to anti-inflammatory phenotype

Cellular Immunology

Volumn 279, Issue 1, 2012, Pages 78-86

  Nujić, Krunoslav ^a   Banjanac, Mihailo ^a,b   Munić, Vesna ^a,b   Polančec, Denis ^a,b   Eraković Haber, Vesna ^a,b  

^a GLAXOSMITHKLINE   (United Kingdom)

^b Galapagos Research Center Zagreb   (Croatia)

Author keywords

Azithromycin; Chloroquine; Concanamycin; Inflammation; Lysosome

Indexed keywords

ARACHIDONIC ACID; AZITHROMYCIN; CHLOROQUINE; CONCANAMYCIN A; PHOSPHOLIPASE; PROSTAGLANDIN E2; TOLL LIKE RECEPTOR 4;

ACIDIFICATION; ANIMAL CELL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; AUTOPHAGY; CELL VACUOLE; ENZYME ACTIVATION; INTRACELLULAR SIGNALING; LYSOSOME; NONHUMAN; PRIORITY JOURNAL; UBIQUITINATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ARACHIDONIC ACID; AZITHROMYCIN; BLOTTING, WESTERN; CELL LINE; CELL SURVIVAL; CHLOROQUINE; DINOPROSTONE; ENZYME INHIBITORS; FLOW CYTOMETRY; HYDROGEN-ION CONCENTRATION; INTERLEUKIN-6; LIPOPOLYSACCHARIDES; LYSOSOMES; MACROLIDES; MACROPHAGES; MICE; MICROSCOPY, CONFOCAL; PROTON-TRANSLOCATING ATPASES; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84871664530     PISSN: 00088749     EISSN: 10902163     Source Type: Journal    
DOI: 10.1016/j.cellimm.2012.09.007     Document Type: Article

References (60)

1. Duvvuri M., Krise J.P. A novel assay reveals that weakly basic model compounds concentrate in lysosomes to an extent greater than pH-partitioning theory would predict. Mol. Pharm. 2005, 2:440-448.
2. Kaufmann A.M., Krise J.P. Lysosomal sequestration of amine-containing drugs: analysis and therapeutic implications. J. Pharm. Sci. 2007, 96:729-746.
3. Alakoskela J.M., Vitovic P., Kinnunen P.K. Screening for the drug-phospholipid interaction: correlation to phospholipidosis. ChemMedChem 2009, 4:1224-1251.
4. Anderson N., Borlak J. Drug-induced phospholipidosis. FEBS Lett. 2006, 580:5533-5540.
5. Vanaudenaerde B.M., Vos R., Meyts I., De Vleeschauwer S.I., Verleden S.E., Widyastuti-Willems A., Wuyts W.A., Van Raemdonck D.E., Hoet P.H., Dupont L.J., Nemery B., Verleden G.M. Macrolide therapy targets a specific phenotype in respiratory medicine: from clinical experience to basic science and back. Inflamm. Allergy Drug Targets 2008, 7:279-287.
6. Shinkai M., Henke M.O., Rubin B.K. Macrolide antibiotics as immunomodulatory medications: proposed mechanisms of action. Pharmacol. Ther. 2008, 117:393-405.
7. Murphy D.M., Forrest I.A., Curran D., Ward C. Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?. Expert Opin. Invest. Drugs 2010, 19:401-414.
8. Culic O., Erakovic V., Parnham M.J. Anti-inflammatory effects of macrolide antibiotics. Eur. J. Pharmacol. 2001, 1-3:209-229.
9. Stamatiou R., Paraskeva E., Boukas K., Gourgoulianis K.I., Molyvdas P.A., Hatziefthimiou A.A. Azithromycin has an antiproliferative and autophagic effect on airway smooth muscle cells. Eur. Respir. J. 2009, 34:721-730.
10. Sugiyama K., Shirai R., Mukae H., Ishimoto H., Nagata T., Sakamoto H., Ishii H., Nakayama S., Yanagihara K., Mizuta Y., Kohno S. Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells. Clin. Exp. Immunol. 2007, 147:540-546.
11. Shinkai M., Foster G.H., Rubin B.K. Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production by human bronchial epithelial cells. Am. J. Physiol Lung Cell Mol. Physiol. 2006, 290:75-85.
12. Halldorsson S., Gudjonsson T., Gottfredsson M., Singh P.K., Gudmundsson G.H., Baldursson O. Azithromycin maintains airway epithelial integrity during Pseudomonas aeruginosa infection. Am. J. Respir. Cell Mol. Biol. 2010, 42:62-68.
13. Stupin Polancec D., Munic Kos V., Banjanac M., Vrancic M., Cuzic S., Belamaric D., Parnham M.J., Polancec D., Erakovic Haber V. Azithromycin drives in vitro GM-CSF/IL-4-induced differentiation of human blood monocytes toward dendritic-like cells with regulatory properties. J. Leukoc. Biol. 2012, 91(2):229-243.
14. Vrancic M., Banjanac M., Nujic K., Bosnar M., Murati T., Munic V., Stupin Polancec D., Belamaric D., Parnham M.J., Erakovic Haber V. Azithromycin distinctively modulates classical activation of human monocytes in vitro. Br. J. Pharmacol. 2012, 165(5):1348-1360.
15. Marjanovic N., Bosnar M., Michielin F., Willé D.R., Anic-Milic T., Culic O., Popovic-Grle S., Bogdan M., Parnham M.J., Erakovic Haber V. Macrolide antibiotics broadly and distinctively inhibit cytokine and chemokine production by COPD sputum cells in vitro. Pharmacol. Res. 2011, 63(5):389-397.
16. Cigana C., Assael B.M., Melotti P. Azithromycin selectively reduces tumor necrosis factor alpha levels in cystic fibrosis airway epithelial cells. Antimicrob. Agents Chemother. 2007, 3:975-981.
17. Cigana C., Nicolis E., Pasetto M., Assael B.M., Melotti P. Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells. Biochem. Biophys. Res. Commun. 2006, 4:977-982.
18. Yamauchi K., Shibata Y., Kimura T., Abe S., Inoue S., Osaka D., Sato M., Igarashi A., Kubota I. Azithromycin suppresses interleukin-12p40 expression in lipopolysaccharide and interferon-gamma stimulated macrophages. Int. J. Biol. Sci. 2009, 7:667-678.
19. Bosnar M., Cuzic S., Bosnjak B., Nujic K., Ergovic G., Marjanovic N., Pasalic I., Hrvacic B., Polancec D., Glojnaric I., Erakovic Haber V. Azithromycin inhibits macrophage interleukin-1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia. Int. Imunopharmacol. 2010, 11(4):424-434.
20. Van B.F., Montenez J.P., Piret J., Tulkens P.M., Courtoy P.J., Mingeot-Leclercq M.P. Interaction of the macrolide azithromycin with phospholipids. I. Inhibition of lysosomal phospholipase A1 activity. Eur. J. Pharmacol. 2006, 1-2:203-214.
21. Abdelghaffar H., Vazifeh D., Labro M.T. Erythromycin A-derived macrolides modify the functional activities of human neutrophils by altering the phospholipase d-phosphatidate phosphohydrolase transduction pathway: l-cladinose is involved both in alterations of neutrophil functions and modulation of this transductional pathway. J. Immunol. 1997, 8:3995-4005.
22. Ikegaya S., Inai K., Iwasaki H., Ueda T. Azithromycin reduces tumor necrosis factor-alpha production in lipopolysaccharide-stimulated THP-1 monocytic cells by modification of stress response and p38 MAPK pathway. J. Chemother. 2009, 21(4):396-402.
23. Immamura Y., Yanagihara K., Mizuta Y., Seki M., Ohno H., Higashiyama Y., Miyazaki Y., Tsukamoto K., Hirakata Y., Tomono K., Kadota J., Kohno S. Azithromycin inhibits MUC5AC production induced by the Pseudomonas aeruginosa autoinducer N-(3-Oxododecanoyl) homoserine lactone in NCI-H292 cells. Antimicrob. Agents Chemother. 2004, 48(9):3457-3461.
24. Berquand A., Fa N., Dufrene Y.F., Mingeot-Leclercq M.P. Interaction of the macrolide antibiotic azithromycin with lipid bilayers: effect on membrane organization, fluidity, and permeability. Pharm. Res. 2005, 3:465-475.
25. Montenez J.P., Van B.F., Piret J., Brasseur R., Tulkens P.M., Mingeot-Leclercq M.P. Interactions of macrolide antibiotics (erythromycin A, roxithromycin, erythromycylamine [Dirithromycin], and azithromycin) with phospholipids: computer-aided conformational analysis and studies on acellular and cell culture models. Toxicol. Appl. Pharmacol. 1999, 2:129-140.
26. Tyteca D., Schanck A., Dufrene Y.F., Deleu M., Courtoy P.J., Tulkens P.M., Mingeot-Leclercq M.P. The macrolide antibiotic azithromycin interacts with lipids and affects membrane organization and fluidity: studies on Langmuir-Blodgett monolayers, liposomes and J774 macrophages. J. Membr. Biol. 2003, 3:203-215.
27. Tyteca D., Van Der S.P., Mettlen M., Van B.F., Tulkens P.M., Mingeot-Leclercq M.P., Courtoy P.J. Azithromycin, a lysosomotropic antibiotic, has distinct effects on fluid-phase and receptor-mediated endocytosis, but does not impair phagocytosis in J774 macrophages. Exp. Cell Res. 2002, 281:86-100.
28. Van B.F., Gerbaux C., Michot J.M., D'Yvoire M.B., Montenez J.P., Tulkens P.M. Lysosomal alterations induced in cultured rat fibroblasts by long-term exposure to low concentrations of azithromycin. J. Antimicrob. Chemother. 1998, 42:761-767.
29. Cooper R.G., Magwere T. Chloroquine: novel uses & manifestations. Indian J. Med. Res. 2008, 127:305-316.
30. Karres I., Kremer J.P., Dietl I., Steckholzer U., Jochum M., Ertel W. Chloroquine inhibits proinflammatory cytokine release into human whole blood. Am. J. Physiol. 1998, 274:1058-1064.
31. Ziegler H.K., Unanue E.R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc. Natl. Acad. Sci. USA 1982, 79:175-178.
32. Misra U.K., Gawdi G., Pizzo S.V. Chloroquine, quinine and quinidine inhibit calcium release from macrophage intracellular stores by blocking inositol 1,4,5-trisphosphate binding to its receptor. J. Cell Biochem. 1997, 64:225-232.
33. Jang C.H., Choi J.H., Byun M.S., Jue D.M. Chloroquine inhibits production of TNF-alpha, IL-1beta and IL-6 from lipopolysaccharide-stimulated human monocytes/macrophages by different modes. Rheumatology (Oxf) 2006, 45:703-710.
34. Bondeson J., Sundler R. Antimalarial drugs inhibit phospholipase A2 activation and induction of interleukin 1beta and tumor necrosis factor alpha in macrophages: implications for their mode of action in rheumatoid arthritis. Gen. Pharmacol. 1998, 30:357-366.
35. Bevan A.P., Krook A., Tikerpae J., Seabright P.J., Siddle K., Smith G.D. Chloroquine extends the lifetime of the activated insulin receptor complex in endosomes. J. Biol. Chem. 1997, 272:26833-26840.
36. Knutson V.P., Ronnett G.V., Lane M.D. The effects of cycloheximide and chloroquine on insulin receptor metabolism. Differential effects on receptor recycling and inactivation and insulin degradation. J. Biol. Chem. 1985, 260:14180-14188.
37. Gonzalez-Noriega A., Grubb J.H., Talkad V., Sly W.S. Chloroquine inhibits lysosomal enzyme pinocytosis and enhances lysosomal enzyme secretion by impairing receptor recycling. J. Cell Biol. 1980, 85:839-852.
38. Graves P.R., Kwiek J.J., Fadden P., Ray R., Hardeman K., Coley A.M., Foley M., Haystead T.A. Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol. Pharmacol. 2002, 62:1364-1372.
39. Munic V., Banjanac M., Kostrun S., Nujic K., Bosnar M., Marjanovic N., Ralic J., Matijasic M., Hlevnjak M., Erakovic Haber V. Intensity of macrolide anti-inflammatory activity in J774A.1 cells positively correlates with cellular accumulation and phospholipidosis. Pharmacol. Res. 2011, 64:298-307.
40. Banjanac M., Munic Kos V., Nujic K., Vrancic M., Belamaric D., Crnkovic S., Hlevnjak M., Erakovic Haber V. Anti-inflammatory mechanism of action of azithromycin in LPS-stimulated J774A.1 cells. Pharmacol. Res. 2012, 66:357-362.
41. Drose S., Altendorf K. Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases. J. Exp. Biol. 1997, 200:1-8.
42. Bosnar M., Bosnjak B., Cuzic S., Hrvacic B., Marjanovic N., Glojnaric I., Culic O., Parnham M.J., Erakovic Haber V. Azithromycin and clarithromycin inhibit lipopolysaccharide-induced murine pulmonary neutrophilia mainly through effects on macrophage-derived granulocyte-macrophage colony-stimulating factor and interleukin-1beta. J. Pharmacol. Exp. Ther. 2009, 331:104-113.
43. Shacka J.J., Klocke B.J., Roth K.A. Autophagy, bafilomycin and cell death: the " a-B-cs" of plecomacrolide-induced neuroprotection. Autophagy 2006, 2(3):228-230.
44. Miggin S.M., O'Neill L.A. New insights into the regulation of TLR signaling. J. Leukoc. Biol. 2006, 80:220-226.
45. Liew F.Y., Xu D., Brint E.K., O'Neill L.A. Negative regulation of toll-like receptor-mediated immune responses. Nat. Rev. Immunol. 2005, 5:446-458.
46. Nujic K., Smith M., Lee M., Belamaric D., Tomaskovic L., Alihodzic S., Malnar I., Polancec D., Schneider K., Erakovic Haber V. Valosin containing protein (VCP) interacts with macrolide antibiotics without mediating their anti-inflammatory activity. Eur. J. Pharmacol. 2012, 677:163-172.
47. Ito K., Kobayashi T., Moriyama Y., Toshima K., Tatsuta K., Kakiuchi T., Futai M., Ploegh H.L., Miwa K. Concanamycin B inhibits the expression of newly-synthesized MHC class II molecules on the cell surface. J. Antibiot. 1995, 48(6):488-494.
48. Hong J., Nakano Y., Yokomakura A., Ishihara K., Kim S., Kang Y.S., Ohuchu K. Nitric oxide production by the vacuolar-type (H+)-ATPase inhibitors bafilomycin A1 and concanamycin A and its possible role in apoptosis in RAW 264.7 cells. J. Pharmacol. Exp. Ther. 2006, 319(2):672-681.
49. Eswarappa S.M., Basu N., Joy O., Chakravortty D. Folimycin (concanamycin A) inhibits LPS-induced nitric oxide production and reduces surface localisation of TLR4 in murine macrophages. Innate Immun. 2008, 14(1):13-24.
50. Hinoki A., Yoshimura K., Fujita K., Akita M., Ikeda R., Nagashima M., Nomura M., Satomi A. Suppression of proinflammatory cytokine production in macrophages by lansoprazole. Pediatr. Surg. Int. 2006, 22(11):915-923.
51. Schulze H., Kolter T., Sandhoff K. Principles of lysosomal membrane degradation: Cellular topology and biochemistry of lysosomal lipid degradation. Biochim. Biophys. Acta 2009, 1793:674-683.
52. Mousavi S.A., Kjeken R., Berg T.O., Seglen P.O., Berg T., Brech A. Effects of inhibitors of the vacuolar proton pump on hepatic heterophagy and autophagy. Biochim. Biophys. Acta 2001, 1510(1-2):243-257.
53. Gerbaux C., Van B.F., Montenez J.P., Piret J., Morlighem G., Tulkens P.M. Hyperactivity of cathepsin B and other lysosomal enzymes in fibroblasts exposed to azithromycin, a dicationic macrolide antibiotic with exceptional tissue accumulation. FEBS Lett. 1996, 394:307-310.
54. Tanida I., Ueno T., Kominami E. LC3 conjugation system in mammalian autophagy. Int. J. Biochem. Cell Biol. 2004, 36:2503-2518.
55. Murphy J.E., Padilla B.E., Hasdemir B., Cottrell G.S., Bunnett N.W. Endosomes: a legitimate platform for the signaling train. Proc. Natl. Acad. Sci. USA 2009, 106:17615-17622.
56. Sanjuan M.A., Milasta S., Green D.R. Toll-like receptor signaling in the lysosomal pathways. Immunol. Rev. 2009, 227:203-220.
57. Lu Y.C., Yeh W.C., Ohashi P.S. LPS/TLR4 signal transduction pathway. Cytokine 2008, 42:145-151.
58. Husebye H., Halaas O., Stenmark H., Tunheim G., Sandanger O., Bogen B., Brech A., Latz E., Espevik T. Endocytic pathways regulate Toll-like receptor 4 signaling and link innate and adaptive immunity. EMBO J. 2006, 25:683-692.
59. Loffler B.M., Bohn E., Hesse B., Kunze H. Effects of antimalarial drugs on phospholipase A and lysophospholipase activities in plasma membrane, mitochondrial, microsomal and cytosolic subcellular fractions of rat liver. Biochim. Biophys. Acta 1985, 835:448-455.
60. Nosal R., Jancinova V. Cationic amphiphilic drugs and platelet phospholipase A(2) (cPLA(2)). Thromb. Res. 2002, 105:339-345.