Clofazimine biocrystal accumulation in macrophages upregulates interleukin 1 receptor antagonist production to induce a systemic anti-inflammatory state

Antimicrobial Agents and Chemotherapy

Volumn 60, Issue 6, 2016, Pages 3470-3479

  Yoon, Gi S ^a   Keswani, Rahul K ^a   Sud, Sudha ^a   Rzeczycki, Phillip M ^a   Murashov, Mikhail D ^a   Koehn, Tony A ^a   Standiford, Theodore J ^b   Stringer, Kathleen A ^a   Rosania, Gus R ^a  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARRAGEENAN; CLOFAZIMINE; INFLAMMASOME; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; LIPOPOLYSACCHARIDE; TUMOR NECROSIS FACTOR ALPHA; ANTIINFLAMMATORY AGENT; IL1B PROTEIN, MOUSE; IL1RAP PROTEIN, MOUSE; INTERLEUKIN 1 RECEPTOR ACCESSORY PROTEIN; TUMOR NECROSIS FACTOR;

ACTIVATION ANALYSIS; ACUTE LUNG INJURY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BIOACCUMULATION; COMPARATIVE STUDY; CONTROLLED STUDY; CRYSTALLIZATION; DRUG ACCUMULATION; DRUG LIVER LEVEL; FOOT EDEMA; FOOT PAD; IMMUNE SYSTEM; IMMUNOMODULATION; INFLAMMATION; KNOCKOUT MOUSE; LUNG; MACROPHAGE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SPLEEN; UPREGULATION; ANIMAL; BIOSYNTHESIS; C57BL MOUSE; DRUG EFFECTS; GENETICS; IMMUNOLOGY; LIVER; METABOLISM; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; CARRAGEENAN; CASPASE 1; CLOFAZIMINE; INFLAMMASOMES; INFLAMMATION; INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN; INTERLEUKIN-1BETA; LIPOPOLYSACCHARIDES; LIVER; LUNG; MACROPHAGES; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; SIGNAL TRANSDUCTION; SPLEEN; TRANSCRIPTIONAL ACTIVATION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84973541572     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00265-16     Document Type: Article

References (62)

1. Barry VC, Belton JG, Conalty ML, Denney JM, Edward DW, O'Sullivan JF, Twomey D, Winder F. 1957. A new series of phenazines (riminocompounds) with high antituberculosis activity. Nature 179:1013-1015. http://dx.doi.org/10.1038/1791013a0.
2. Cholo MC, Steel HC, Fourie PB, Germishuizen WA, Anderson R. 2012. Clofazimine: current status and future prospects. J Antimicrob Chemother 67:290-298. http://dx.doi.org/10.1093/jac/dkr444.
3. Reibel F, Cambau E, Aubry A. 2015. Update on the epidemiology, diagnosis, and treatment of leprosy. Med Mal Infect 45:383-393. http://dx.doi.org/10.1016/j.medmal.2015.09.002.
4. Tyagi S, Ammerman NC, Li S-Y, Adamson J, Converse PJ, Swanson RV, Almeida DV, Grosset JH. 2015. Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis. Proc Natl Acad Sci USA 112:869-874. http://dx.doi.org/10.1073/pnas.1416951112.
5. Lechartier B, Cole ST. 2015. Mode of action of clofazimine and combination therapy with benzothiazinones against Mycobacterium tuberculosis. Antimicrob Agents Chemother 59:4457-4463. http://dx.doi.org/10.1128/AAC.00395-15.
6. Williams K, Minkowski A, Amoabeng O, Peloquin CA, Taylor D, Andries K, Wallis RS, Mdluli KE, Nuermberger EL. 2012. Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother 56:3114-3120. http://dx.doi.org/10.1128/AAC.00384-12.
7. Banerjee DK, Ellard GA, Gammon PT, Waters MF. 1974. Some observations on the pharmacology of clofazimine (B663). Am J Trop Med Hyg 23:1110-1115.
8. Baik J, Stringer KA, Mane G, Rosania GR. 2013. Multiscale distribution and bioaccumulation analysis of clofazimine reveals a massive immune system-mediated xenobiotic sequestration response. Antimicrob Agents Chemother 57:1218-1230. http://dx.doi.org/10.1128/AAC.01731-12.
9. Keswani RK, Baik J, Yeomans L, Hitzman C, Johnson AM, Pawate AS, Kenis PJA, Rodriguez-Hornedo N, Stringer KA, Rosania GR. 2015. Chemical analysis of drug biocrystals: a role for counterion transport pathways in intracellular drug disposition. Mol Pharm 12:2528-2536. http://dx.doi.org/10.1021/acs.molpharmaceut.5b00032.
10. Harbeck RJ, Worthen GS, Lebo TD, Peloquin CA. 1999. Clofazimine crystals in the cytoplasm of pulmonary macrophages. Ann Pharmacother 33:250. http://dx.doi.org/10.1345/aph.18170.
11. Sukpanichnant S, Hargrove NS, Kachintorn U, Manatsathit S, Chan-chairujira T, Siritanaratkul N, Akaraviputh T, Thakerngpol K. 2000. Clofazimine-induced crystal-storing histiocytosis producing chronic abdominal pain in a leprosy patient. Am J Surg Pathol 24:129-135. http://dx.doi.org/10.1097/00000478-200001000-00016.
12. Jadhav MV, Sathe AG, Deore SS, Patil PG, Joshi NG, Joghi NG. 2004. Tissue concentration, systemic distribution, and toxicity of clofazimine: an autopsy study. Indian J Pathol Microbiol 47:281-283.
13. Tall AR, Yvan-Charvet L. 2015. Cholesterol, inflammation and innate immunity. Nat Rev Immunol 15:104-116. http://dx.doi.org/10.1038/nri3793.
14. Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440:237-241. http://dx.doi.org/10.1038/nature04516.
15. Gehring U, Wijga AH, Brauer M, Fischer P, de Jongste JC, Kerkhof M, Oldenwening M, Smit HA, Brunekreef B. 2010. Traffic-related air pollution and the development of asthma and allergies during the first 8 years of life. Am J Respir Crit Care Med 181:596-603. http://dx.doi.org/10.1164/rccm.200906-0858OC.
16. Sint T, Donohue JF, Ghio AJ. 2008. Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease. Inhal Toxicol 20:25-29. http://dx.doi.org/10.1080/08958370701758759.
17. Mackey JP, Barnes J. 1974. Clofazimine in the treatment of discoid lupus erythematosus. Br J Dermatol 91:93-96. http://dx.doi.org/10.1111/j.1365-2133.1974.tb06723.x.
18. Lo JS, Berg RE, Tomecki KJ. 1989. Treatment of discoid lupus erythematosus. Int J Dermatol 28:497-507. http://dx.doi.org/10.1111/j.1365-4362.1989.tb04599.x.
19. Chuaprapaisilp T, Piamphongsant T. 1978. Treatment of pustular psoriasis with clofazimine. Br J Dermatol 99:303-305. http://dx.doi.org/10.1111/j.1365-2133.1978.tb02001.x.
20. Podmore P, Burrows D. 1986. Clofazimine: an effective treatment for Melkersson-Rosenthal syndrome or Miescher's cheilitis. Clin Exp Dermatol 11:173-178. http://dx.doi.org/10.1111/j.1365-2230.1986.tb00443.x.
21. Medeiros Bezerra EL, Pereira Vilar MJ, Da Trindade Neto PB, Sato EI. 2005. Double-blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus. Arthritis Rheum 52:3073-3078. http://dx.doi.org/10.1002/art.21358.
22. Venkateswarlu B, Venkataramana D, Rao AV, Prabhakar MC, Reddy BM. 1992. Role of rifampin and clofazimine ointments in the treatment of leprosy. Int J Lepr Other Mycobact Dis 60:269-270.
23. Yoon GS, Sud S, Keswani RK, Baik J, Standiford TJ, Stringer KA, Rosania GR. 2015. Phagocytosed clofazimine biocrystals can modulate innate immune signaling by inhibiting TNF-α and boosting IL-1RA secretion. Mol Pharm 12:2517-2527. http://dx.doi.org/10.1021/acs.molpharmaceut.5b00035.
24. Baik J, Rosania GR. 2011. Molecular imaging of intracellular drugmembrane aggregate formation. Mol Pharm 8:1742-1749. http://dx.doi.org/10.1021/mp200101b.
25. Otterness IG, Moore PF. 1988. Immunochemical techniques. L. Chemotaxis and inflammation. In Methods enzymology. Elsevier, New York, NY.
26. Matute-Bello G, Frevert CW, Martin TR. 2008. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 295:L379-L399. http://dx.doi.org/10.1152/ajplung.00010.2008.
27. Lax S, Wilson MR, Takata M, Thickett DR. 2014. Using a noninvasive assessment of lung injury in a murine model of acute lung injury. BMJ Open Respir Res 1:e000014. http://dx.doi.org/10.1136/bmjresp-2013-000014.
28. Nayak S, Doerfler PA, Porvasnik SL, Cloutier DD, Khanna R, Valenzano KJ, Herzog RW, Byrne BJ. 2014. Immune responses and hypercoagulation in ERT for Pompe disease are mutation and rhGAA dose dependent. PLoS One 9:e98336. http://dx.doi.org/10.1371/journal.pone.0098336.
29. Toth LA. 2000. Defining the moribund condition as an experimental endpoint for animal research. ILAR J 41:72-79. http://dx.doi.org/10.1093/ilar.41.2.72.
30. Nemzek JA, Xiao H-Y, Minard AE, Bolgos GL, Remick DG. 2004. Humane endpoints in shock research. Shock 21:17-25. http://dx.doi.org/10.1097/00024382-200403001-00067.
31. Baik J, Rosania GR. 2012. Macrophages sequester clofazimine in an intracellular liquid crystal-like supramolecular organization. PLoS One 7:e47494. http://dx.doi.org/10.1371/journal.pone.0047494.
32. Keswani RK, Yoon GS, Sud S, Stringer KA, Rosania GR. 2015. A far-red fluorescent probe for flow cytometry and image-based functional studies of xenobiotic sequestering macrophages. Cytometry A 87:855-867. http://dx.doi.org/10.1002/cyto.a.22706.
33. Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E. 2010. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464:1357-1361. http://dx.doi.org/10.1038/nature08938.
34. Ioannou GN, Haigh WG, Thorning D, Savard C. 2013. Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis. J Lipid Res 54:1326-1334. http://dx.doi.org/10.1194/jlr.M034876.
35. Simard J-C, Vallieres F, de Liz R, Lavastre V, Girard D. 2015. Silver nanoparticles induce degradation of the endoplasmic reticulum stress sensor activating transcription factor-6 leading to activation of the NLRP-3 inflammasome. J Biol Chem 290:5926-5939. http://dx.doi.org/10.1074/jbc.M114.610899.
36. Demento SL, Eisenbarth SC, Foellmer HG, Platt C, Caplan MJ, Mark Saltzman W, Mellman I, Ledizet M, Fikrig E, Flavell RA, Fahmy TM. 2009. Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 27:3013-3021. http://dx.doi.org/10.1016/j.vaccine.2009.03.034.
37. Peeters PM, Eurlings IMJ, Perkins TN, Wouters EF, Schins RPF, Borm PJA, Drommer W, Reynaert NL, Albrecht C. 2014. Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs. Part Fibre Toxicol 11:58. http://dx.doi.org/10.1186/s12989-014-0058-0.
38. Gabay C, Smith MF, Eidlen D, Arend WP. 1997. Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein. J Clin Invest 99:2930-2940. http://dx.doi.org/10.1172/JCI119488.
39. Gabay C, Gigley J, Sipe J, Arend WP, Fantuzzi G. 2001. Production of IL-1 receptor antagonist by hepatocytes is regulated as an acute-phase protein in vivo. Eur J Immunol 31:490-499. http://dx.doi.org/10.1002/1521-4141(200102)31:2〈490::AID-IMMU490〉3.0.CO;2-H.
40. Dinarello CA, van der Meer JWM. 2013. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol 25:469-484. http://dx.doi.org/10.1016/j.smim.2013.10.008.
41. Arend WP. 2002. The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev 13:323-340. http://dx.doi.org/10.1016/S1359-6101(02)00020-5.
42. McDougall AC, Horsfall WR, Hede JE, Chaplin AJ. 1980. Splenic infarction and tissue accumulation of crystals associated with the use of clofazimine (Lamprene; B663) in the treatment of pyoderma gangrenosum. Br J Dermatol 102:227-230. http://dx.doi.org/10.1111/j.1365-2133.1980.tb05697.x.
43. Shi Y, Mucsi AD, Ng G. 2010. Monosodium urate crystals in inflammation and immunity. Immunol Rev 233:203-217. http://dx.doi.org/10.1111/j.0105-2896.2009.00851.x.
44. Riteau N, Baron L, Villeret B, Guillou N, Savigny F, Ryffel B, Rassendren F, Le Bert M, Gombault A, Couillin I. 2012. ATP release and purinergic signaling: a common pathway for particle-mediated inflammasome activation. Cell Death Dis 3:e403. http://dx.doi.org/10.1038/cddis.2012.144.
45. Bulakh PM, Kowale CN, Ranade SM, Burte NP, Chandorkar AG. 1983. The effect of clofazimine on liver function tests in lepra reaction (ENL). Lepr India 55:714-718.
46. Cariello PF, Kwak EJ, Abdel-Massih RC, Silveira FP. 2015. Safety and tolerability of clofazimine as salvage therapy for atypical mycobacterial infection in solid organ transplant recipients. Transpl Infect Dis 17:111-118. http://dx.doi.org/10.1111/tid.12340.
47. Kaluarachchi SI, Fernandopulle BM, Gunawardane BP. 2001. Hepatic and haematological adverse reactions associated with the use of multidrug therapy in leprosy: a five year retrospective study. Indian J Lepr 73:121-129.
48. Gent S, Kleinbongard P, Dammann P, Neuhäuser M, Heusch G. 2015. Heart rate reduction and longevity in mice. Basic Res Cardiol 110:2. http://dx.doi.org/10.1007/s00395-014-0460-7.
49. Stokes WS. 2002. Humane endpoints for laboratory animals used in regulatory testing. ILAR J 43(Suppl):S31-S38.
50. Van Rensburg CE, Jooné GK, O'Sullivan JF, Anderson R. 1992. Antimicrobial activities of clofazimine and B669 are mediated by lysophospholipids. Antimicrob Agents Chemother 36:2729-2735. http://dx.doi.org/10.1128/AAC.36.12.2729.
51. Oliva B, O'Neill AJ, Miller K, Stubbings W, Chopra I. 2004. Antistaphylococcal activity and mode of action of clofazimine. J Antimicrob Chemother 53:435-440. http://dx.doi.org/10.1093/jac/dkh114.
52. Fulda S, Gorman AM, Hori O, Samali A. 2010. Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010:214074.
53. Kroemer G, Mariño G, Levine B. 2010. Autophagy and the integrated stress response. Mol Cell 40:280-293. http://dx.doi.org/10.1016/j.molcel.2010.09.023.
54. Fukutomi Y, Maeda Y, Makino M. 2011. Apoptosis-inducing activity of clofazimine in macrophages. Antimicrob Agents Chemother 55:4000-4005. http://dx.doi.org/10.1128/AAC.00434-11.
55. Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A. 2009. A gene network regulating lysosomal biogenesis and function. Science 325:473-477. http://dx.doi.org/10.1126/science.1174447.
56. Logan R, Kong AC, Krise JP. 2014. Time-dependent effects of hydrophobic amine-containing drugs on lysosome structure and biogenesis in cultured human fibroblasts. J Pharm Sci 103:3287-3296. http://dx.doi.org/10.1002/jps.24087.
57. Parks A, Charest-Morin X, Boivin-Welch M, Bouthillier J, Marceau F. 2015. Autophagic flux inhibition and lysosomogenesis ensuing cellular capture and retention of the cationic drug quinacrine in murine models. PeerJ 3:e1314. http://dx.doi.org/10.7717/peerj.1314.
58. Zhitomirsky B, Assaraf YG. 2015. Lysosomal sequestration of hydrophobic weak base chemotherapeutics triggers lysosomal biogenesis and lysosome-dependent cancer multidrug resistance. Oncotarget 6:1143-1156. http://dx.doi.org/10.18632/oncotarget.2732.
59. Emanuel R, Sergin I, Bhattacharya S, Turner JN, Epelman S, Settembre C, Diwan A, Ballabio A, Razani B. 2014. Induction of lysosomal biogenesis in atherosclerotic macrophages can rescue lipid-induced lysosomal dysfunction and downstream sequelae. Arterioscler Thromb Vasc Biol 34:1942-1952. http://dx.doi.org/10.1161/ATVBAHA.114.303342.
60. Hasegawa H. 2013. Aggregates, crystals, gels, and amyloids: intracellular and extracellular phenotypes at the crossroads of immunoglobulin physicochemical property and cell physiology. Int J Cell Biol 2013:604867.
61. Hasegawa H, Wendling J, He F, Trilisky E, Stevenson R, Franey H, Kinderman F, Li G, Piedmonte DM, Osslund T, Shen M, Ketchem RR. 2011. In vivo crystallization of human IgG in the endoplasmic reticulum of engineered Chinese hamster ovary (CHO) cells. J Biol Chem 286: 19917-19931. http://dx.doi.org/10.1074/jbc.M110.204362.
62. Bettigole SE, Glimcher LH. 2015. Endoplasmic reticulum stress in immunity. Annu Rev Immunol 33:107-138. http://dx.doi.org/10.1146/annurev-immunol-032414-112116.