Article thumbnail

Potential Role of the Inflammasome-Derived Inflammatory Cytokines in Pulmonary Fibrosis

By Rupa Biswas, Melisa Bunderson-Schelvan and Andrij Holian

Abstract

Pulmonary fibrosis is a progressive, disabling disease with mortality rates that appear to be increasing in the western population, including the USA. There are over 140 known causes of pulmonary fibrosis as well as many unknown causes. Treatment options for this disease are limited due to poor understanding of the molecular mechanisms of the disease progression. However, recent progress in inflammasome research has greatly contributed to our understanding of its role in inflammation and fibrosis development. The inflammasome is a multiprotein complex that is an important component of both the innate and adaptive immune systems. Activation of proinflammatory cytokines following inflammasome assembly, such as IL-1β and IL-18, has been associated with development of PF. In addition, components of the inflammasome complex itself, such as the adaptor protein ASC have been associated with PF development. Recent evidence suggesting that the fibrotic process can be reversed via blockade of pathways associated with inflammasome activity may provide hope for future drug strategies. In this paper we will give an introduction to pulmonary fibrosis and its known causes. In addition, we will discuss the importance of the inflammasome in the development of pulmonary fibrosis as well as discuss potential future treatment options

Topics: Review Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3109309
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (1992). A .L .O l s o n ,J .J .S w i g r i s ,D .C .L e z o t t e ,J .M .N o r r i s
  2. (2010). A.GogaliandA.U.Wells,“Newpharmacologicalstrategiesfor the treatment of pulmonary fibrosis,”
  3. (2007). Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene expression pattern,”
  4. (2010). Adenosine in fibrosis,”
  5. (2009). Advances in understanding of idiopathic pulmonary fibrosis,”
  6. (2010). Alexander et al., “Association of FcγRIIa R131H polymorphism with idiopathic pulmonary fibrosis severity and progression,”
  7. (2008). Approaching the degradome in idiopathic pulmonary fibrosis,”
  8. (2009). Asanuma et al., “IL18 neutralization ameliorates obstruction-induced epithelialmesenchymal transition and renal fibrosis,”
  9. Azithromycin reduces pulmonary fibrosis in a bleomycin mouse model,” ExperimentalLungResearch,vol.36,no.10,pp.602–614,2010.
  10. (1996). Biologic basis for interleukin-1 in disease,”
  11. (2006). Chemokine/cytokine cocktail in idiopathic pulmonary fibrosis,”
  12. (2010). Clinic: Education and Research,
  13. (2003). Critical role for cathepsin B in mediating caspase-1-dependent interleukin-18 maturation and caspase-1-independent necrosis triggered by the microbial toxin nigericin,”
  14. (2009). Determinants of initiation and progression of idiopathic pulmonary fibrosis,”
  15. (2009). Elevated asymmetric dimethylarginine alters lung function and induces collagen deposition in mice,”
  16. (2004). Essentials of Medical Pharmacology,J a y p e e
  17. (2005). Familial idiopathic pulmonary fibrosis: clinical features and outcome,”
  18. (1995). G.W.HunninghakeandA.R.Kalica,“Approachestothetreatment of pulmonary fibrosis,”
  19. (2002). Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans,”
  20. (2000). Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement,”
  21. (2006). Idiopathic pulmonary fibrosis: is it a familial disease?”
  22. (2008). IL-13 receptor α2 selectively inhibits IL-13-induced responses in the murine lung,”
  23. (1999). IL-18: at-inducing, proinflammatory cytokine and new member of the IL-1 family,”
  24. (2007). IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice,”
  25. (2009). Immunological and inflammatory functions of the interleukin-1 family,”
  26. (2010). Inflammasome and IL1β-mediated disorders,” Current Allergy and Asthma Reports,
  27. (2008). Inflammatory cytokines augments TGF-β1-induced epithelial-mesenchymal transition in A549 cells by upregulating TβR-I,”
  28. (2007). Inflammatory cytokines induce the transformation of human dermal microvascularendothelialcellsintomyofibroblasts:apotential role in skin fibrogenesis,”
  29. (2010). Innate immune processes are sufficient for driving silicosis in mice,”
  30. (1993). Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica,’’
  31. (2009). Interleukin-1 participates in the progression from liver injury to fibrosis,”
  32. (2003). Interleukin-1-receptor antagonist in the Muckle-Wells syndrome,”
  33. (1998). Interleukin-1β, interleukin-18, and the interleukin-1β converting enzyme,”
  34. (2004). Interstitial lung disease induced by drugs and radiation,”
  35. (2010). Intravascular danger signals guide neutrophils to sites of sterile inflammation,”
  36. (2002). J.A.Belperio,M.Dy,M.D.Burdicketal.,“InteractionofIL-13 andC10inthepathogenesisofbleomycin-inducedpulmonary fibrosis,”
  37. (2010). l b o n i ,D .C e r v i a ,S .S u g a m a ,a n dB .C o n t i ,“ I n t e r l e u k i n1 8 in the CNS,”
  38. (1989). Lysosomal movements during heterophagy and autophagy: with special reference to nematolysosome and wrapping lysosome,”
  39. (2004). Lysosomes in cell death,”
  40. (2010). Molecular mechanism of NLRP3 inflammasome activation,”
  41. (2008). Mossman,andJ.Tschopp,“Innateimmuneactivationthrough Nalp3 inflammasome sensing of asbestos and silica,”
  42. (2003). NF-κB protects from the lysosomal pathway of cell death,”
  43. (2010). Non-steroid agents for idiopathic pulmonary fibrosis,” Cochrane database of systematic reviews
  44. (2011). Novel therapeutic approaches for pulmonary fibrosis,”
  45. (2010). oa n dA .O l i v´ e,
  46. (2008). P.BoyaandG.Kroemer,“Lysosomalmembranepermeabilization in cell death,”
  47. (2011). Paintal et al., “Differential expression of monocyte/macrophage-selective markers in human idiopathic pulmonary fibrosis,”
  48. (2009). Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity,” Particle and Fibre Toxicology,
  49. (2010). Pulmonary Fibrosis Foundation,
  50. (2009). Pulmonary fibrosis: pathogenesis, etiology and regulation,”
  51. (2008). r o e l l ,S .J .R i e d l ,J .H .F r i t z ,A .M .R o j a s ,a n dR . Schwarzenbacher, “The Nod-Like Receptor (NLR) family: a tale of similarities and differences,”
  52. (1999). Rheumatoid arthritis associated with methotrexateinduced pneumonitis: improvement with i.v. cyclophosphamide therapy,” Clinical and Experimental Rheumatology,
  53. (2006). Role of early growth response-1 (Egr-1) in interleukin-13-induced inflammation and remodeling,”
  54. (1997). S i m e ,Z .X i n g ,F .L .G r a h a m ,K .G .C s a k y ,a n dJ .G a u l d i e , “Adenovector-mediated gene transfer of active transforming growth factor- β1 induces prolonged severe fibrosis in rat lung,”
  55. (2009). Sensing pathogens and danger signals by the inflammasome,”
  56. (2004). Serine protease inhibitor 2A inhibits caspase-independent cell death,”
  57. (2008). Silica binding andtoxicityinalveolarmacrophages,”FreeRadicalBiologyand Medicine,
  58. (2008). Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization,”
  59. (2001). T h o m e e r ,U .C o s t a b e l ,G .R i z z a t o ,V .P o l e t t i ,a n d M. Demedts, “Comparison of registries of interstitial lung diseases in three European countries,”
  60. (2010). Technical advance: caspase1 activation and IL-1β release correlate with the degree of lysosome damage, as illustrated by a novel imaging method to quantify phagolysosome damage,” J o u r n a lo fL e u k o c y t e Biology,
  61. (1984). The alveolar macrophage,”
  62. (2010). The effect of surface modification of amorphous silica particles on
  63. (2006). The inflammasome—a linebacker of innate defense,”
  64. (2009). The inflammasome: a caspase-1-activation platform that regulatesimmuneresponsesanddiseasepathogenesis,”Nature Immunology,
  65. (2002). The myofibroblast in pulmonary fibrosis,”
  66. (2008). The Nalp3 inflammasome is essential for the development of silicosis,”
  67. (1996). The role of cytokines in human lung fibrosis,” Monaldi Archives for Chest Disease,
  68. (2010). The role of interleukin-1 in wound biology. part II: in vivo and human translational studies,”
  69. (2008). Tjwa et al., “Fibrinogen drives dystrophic muscle fibrosis via a TGFβ/alternative macrophage activation pathway,”
  70. (2006). Toxic potential of materialsatthenanolevel,”Science,vol.311,no.5761,pp.622– 627,
  71. (2010). Update on macrophage clearance of inhaled micro- and nanoparticles,”
  72. Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis,”
  73. (1995). v a nd e rV e e n ,J .J .D e k k e r ,H .J .D i n a n t ,R .M .v a n Soesbergen,