Frontiers in Biology

, 6:274 | Cite as

An overview of inflammation: mechanism and consequences

  • Afsar U. AhmedEmail author


Inflammation is an essential response provided by the immune systems that ensures the survival during infection and tissue injury. Inflammatory responses are essential for the maintenance of normal tissue homeostasis. The molecular mechanism of inflammation is quite a complicated process which is initiated by the recognition of specific molecular patterns associated with either infection or tissue injury. The entire process of the inflammatory response is mediated by several key regulators involved in the selective expression of proinflammatory molecules. Prolonged inflammations are often associated with severe detrimental side effects on health. Alterations in inflammatory responses due to persistent inducers or genetic variations are on the rise over the last couple of decades, causing a variety of inflammatory diseases and pathophysiological conditions.


Inflammation inflammatory diseases proinflammatory cytokines pattern-recognition receptors transcription factors and chromatin structure 


  1. Aggarwal B B, Vijayalekshmi R V, Sung B (2009). Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res, 15(2): 425–430PubMedCrossRefGoogle Scholar
  2. Akira S, Uematsu S, Takeuchi O (2006). Pathogen recognition and innate immunity. Cell, 124(4): 783–801PubMedCrossRefGoogle Scholar
  3. Amir-Zilberstein L, Ainbinder E, Toube L, Yamaguchi Y, Handa H, Dikstein R (2007). Differential regulation of NF-kappaB by elongation factors is determined by core promoter type. Mol Cell Biol, 27(14): 5246–5259PubMedCrossRefGoogle Scholar
  4. Barnes P J (2009). Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc, 6(8): 693–696PubMedCrossRefGoogle Scholar
  5. Bayarsaihan D (2011). Epigenetic mechanisms in inflammation. J Dent Res, 90(1): 9–17PubMedCrossRefGoogle Scholar
  6. Bohmann D, Bos T J, Admon A, Nishimura T, Vogt P K, Tjian R (1987). Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science, 238(4832): 1386–1392PubMedCrossRefGoogle Scholar
  7. Bosisio D, Marazzi I, Agresti A, Shimizu N, Bianchi M E, Natoli G (2006). A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-kappaB-dependent gene activity. EMBO J, 25(4): 798–810PubMedCrossRefGoogle Scholar
  8. Brownell J E, Zhou J, Ranalli T, Kobayashi R, Edmondson D G, Roth S Y, Allis C D (1996). Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell, 84(6): 843–851PubMedCrossRefGoogle Scholar
  9. Carey MF, Peterson C L, Smale S T 2009. Transcriptional Regulation in Eukaryotes: Concepts, Strategies, and Techniques. New York: Cold Spring Harbor Laboratory PressGoogle Scholar
  10. Cote J, Quinn J, Workman J L, Peterson C L (1994). Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science, 265(5168): 53–60PubMedCrossRefGoogle Scholar
  11. Dalton S, Treisman R (1992). Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell, 68(3): 597–612PubMedCrossRefGoogle Scholar
  12. de Martel C, Franceschi S (2009). Infections and cancer: established associations and new hypotheses. Crit Rev Oncol Hematol, 70(3): 183–194PubMedCrossRefGoogle Scholar
  13. De Santa F, Totaro M G, Prosperini E, Notarbartolo S, Testa G, Natoli G (2007). The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell, 130(6): 1083–1094PubMedCrossRefGoogle Scholar
  14. de Visser K E, Eichten A, Coussens LM (2006). Paradoxical roles of the immune system during cancer development. Nat Rev Cancer, 6(1): 24–37PubMedCrossRefGoogle Scholar
  15. Fakhouri F, Frémeaux-Bacchi V, Noël L H, Cook H T, Pickering M C (2010). C3 glomerulopathy: a new classification. Nat Rev Nephrol, 6(8): 494–499PubMedCrossRefGoogle Scholar
  16. Garrett W S, Gordon J I, Glimcher L H (2010). Homeostasis and inflammation in the intestine. Cell, 140(6): 859–870PubMedCrossRefGoogle Scholar
  17. Ghosh S, May M J, Kopp E B (1998). NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol, 16(1): 225–260PubMedCrossRefGoogle Scholar
  18. Glass C K, Saijo K, Winner B, Marchetto M C, Gage F H (2010). Mechanisms underlying inflammation in neurodegeneration. Cell, 140(6): 918–934PubMedCrossRefGoogle Scholar
  19. Greenberg M E, Ziff E B (1984). Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature, 311(5985): 433–438PubMedCrossRefGoogle Scholar
  20. Grivennikov S I, Greten F R, Karin M (2010). Immunity, inflammation, and cancer. Cell, 140(6): 883–899PubMedCrossRefGoogle Scholar
  21. Hager G L, McNally J G, Misteli T (2009). Transcription dynamics. Mol Cell, 35(6): 741–753PubMedCrossRefGoogle Scholar
  22. Hargreaves D C, Horng T, Medzhitov R (2009). Control of inducible gene expression by signal-dependent transcriptional elongation. Cell, 138(1): 129–145PubMedCrossRefGoogle Scholar
  23. Hollingsworth J W, Siegel E R, Creasey W A (1967). Granulocyte survival in synovial exudate of patients with rheumatoid arthritis and other inflammatory joint diseases. Yale J Biol Med, 39(5): 289–296PubMedGoogle Scholar
  24. Honda K, Takaoka A, Taniguchi T (2006). Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity, 25(3): 349–360PubMedCrossRefGoogle Scholar
  25. Hotamisligil G S (2006). Inflammation and metabolic disorders. Nature, 444(7121): 860–867PubMedCrossRefGoogle Scholar
  26. Imai Y, Kuba K, Neely G G, Yaghubian-Malhami R, Perkmann T, van Loo G, Ermolaeva M, Veldhuizen R, Leung Y H, Wang H, Liu H, Sun Y, Pasparakis M, Kopf M, Mech C, Bavari S, Peiris J S, Slutsky A S, Akira S, Hultqvist M, Holmdahl R, Nicholls J, Jiang C, Binder C J, Penninger J M (2008). Identification of oxidative stress and Tolllike receptor 4 signaling as a key pathway of acute lung injury. Cell, 133(2): 235–249PubMedCrossRefGoogle Scholar
  27. Imbalzano A N, Kwon H, Green M R, Kingston R E (1994). Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature, 370(6489): 481–485PubMedCrossRefGoogle Scholar
  28. Koch M A, Tucker-Heard G, Perdue N R, Killebrew J R, Urdahl K B, Campbell D J (2009). The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol, 10(6): 595–602PubMedCrossRefGoogle Scholar
  29. Kovesdi I, Reichel R, Nevins J R (1986). Identification of a cellular transcription factor involved in E1A trans-activation. Cell, 45(2): 219–228PubMedCrossRefGoogle Scholar
  30. Kumar V, Carey M, Robbins S L 2003. Robbins Basic Pathology. 7th edition. New York: SaundersGoogle Scholar
  31. Kwon H, Imbalzano A N, Khavari P A, Kingston R E, Green M R (1994). Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature, 370(6489): 477–481PubMedCrossRefGoogle Scholar
  32. Lai D, Wan M, Wu J, Preston-Hurlburt P, Kushwaha R, Grundström T, Imbalzano A N, Chi T (2009). Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling. Proc Natl Acad Sci USA, 106(4): 1169–1174PubMedCrossRefGoogle Scholar
  33. Lin W W, Karin M (2007). A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest, 117(5): 1175–1183PubMedCrossRefGoogle Scholar
  34. Liu G, Friggeri A, Yang Y, Park Y J, Tsuruta Y, Abraham E (2009). miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc Natl Acad Sci USA, 106(37): 15819–15824PubMedCrossRefGoogle Scholar
  35. Locksley R M (2010). Asthma and allergic inflammation. Cell, 140(6): 777–783PubMedCrossRefGoogle Scholar
  36. Luger K, Mäder A W, Richmond R K, Sargent D F, Richmond T J (1997). Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature, 389(6648): 251–260PubMedCrossRefGoogle Scholar
  37. Maeda S, Kamata H, Luo J L, Leffert H, Karin M (2005). IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell, 121(7): 977–990PubMedCrossRefGoogle Scholar
  38. Majno G, Joris I 2004. Cells, Tissues, and Diseases. Second Edition. Oxford: Oxford University PressGoogle Scholar
  39. Mantovani A, Allavena P, Sica A, Balkwill F (2008). Cancer-related inflammation. Nature, 454(7203): 436–444PubMedCrossRefGoogle Scholar
  40. Medzhitov R (2007). Recognition of microorganisms and activation of the immune response. Nature, 449(7164): 819–826PubMedCrossRefGoogle Scholar
  41. Medzhitov R (2008). Origin and physiological roles of inflammation. Nature, 454(7203): 428–435PubMedCrossRefGoogle Scholar
  42. Medzhitov R (2010). Inflammation 2010: new adventures of an old flame. Cell, 140(6): 771–776PubMedCrossRefGoogle Scholar
  43. Montminy M R, Bilezikjian L M (1987). Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature, 328(6126): 175–178PubMedCrossRefGoogle Scholar
  44. Munshi N, Agalioti T, Lomvardas S, Merika M, Chen G, Thanos D (2001). Coordination of a transcriptional switch by HMGI(Y) acetylation. Science, 293(5532): 1133–1136PubMedCrossRefGoogle Scholar
  45. Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, Ichinose M, Tatematsu M, Ushijima T (2010). Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res, 70(4): 1430–1440PubMedCrossRefGoogle Scholar
  46. Okazaki I M, Kotani A, Honjo T (2007). Role of AID in tumorigenesis. Adv Immunol, 94: 245–273PubMedCrossRefGoogle Scholar
  47. Ouyang W, Kolls J K, Zheng Y (2008). The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity, 28(4): 454–467PubMedCrossRefGoogle Scholar
  48. Panne D, Maniatis T, Harrison S C (2004). Crystal structure of ATF-2/c-Jun and IRF-3 bound to the interferon-beta enhancer. EMBO J, 23(22): 4384–4393PubMedCrossRefGoogle Scholar
  49. Panne D, Maniatis T, Harrison S C (2007). An atomic model of the interferon-beta enhanceosome. Cell, 129(6): 1111–1123PubMedCrossRefGoogle Scholar
  50. Prywes R, Roeder R G (1986). Inducible binding of a factor to the c-fos enhancer. Cell, 47(5): 777–784PubMedCrossRefGoogle Scholar
  51. Ramirez-Carrozzi V R, Braas D, Bhatt D M, Cheng C S, Hong C, Doty K R, Black J C, Hoffmann A, Carey M, Smale S T (2009). A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell, 138(1): 114–128PubMedCrossRefGoogle Scholar
  52. Ramirez-Carrozzi V R, Nazarian A A, Li C C, Gore S L, Sridharan R, Imbalzano A N, Smale S T (2006). Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev, 20(3): 282–296PubMedCrossRefGoogle Scholar
  53. Robinson D S, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley A M, Corrigan C, Durham S R, Kay A B (1992). Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med, 326(5): 298–304PubMedCrossRefGoogle Scholar
  54. Rogers A J, Raby B A, Lasky-Su J A, Murphy A, Lazarus R, Klanderman B J, Sylvia J S, Ziniti J P, Lange C, Celedón J C, Silverman E K, Weiss S T (2009). Assessing the reproducibility of asthma candidate gene associations, using genome-wide data. Am J Respir Crit Care Med, 179(12): 1084–1090PubMedCrossRefGoogle Scholar
  55. Rubtsov Y P, Rasmussen J P, Chi E Y, Fontenot J, Castelli L, Ye X, Treuting P, Siewe L, Roers A, Henderson W R Jr, Muller W, Rudensky A Y (2008). Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity, 28(4): 546–558PubMedCrossRefGoogle Scholar
  56. Saccani S, Natoli G (2002). Dynamic changes in histone H3 Lys 9 methylation occurring at tightly regulated inducible inflammatory genes. Genes Dev, 16(17): 2219–2224PubMedCrossRefGoogle Scholar
  57. Saccani S, Pantano S, Natoli G (2001). Two waves of nuclear factor kappaB recruitment to target promoters. J Exp Med, 193(12): 1351–1359PubMedCrossRefGoogle Scholar
  58. Sakurai T, He G, Matsuzawa A, Yu G Y, Maeda S, Hardiman G, Karin M (2008). Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell, 14(2): 156–165PubMedCrossRefGoogle Scholar
  59. Sen R, Baltimore D (1986). Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell, 47(6): 921–928PubMedCrossRefGoogle Scholar
  60. Serhan C N, Savill J (2005). Resolution of inflammation: the beginning programs the end. Nat Immunol, 6(12): 1191–1197PubMedCrossRefGoogle Scholar
  61. Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A, Soreq H (2009). MicroRNA-132 potentiates cholinergic antiinflammatory signaling by targeting acetylcholinesterase. Immunity, 31(6): 965–973PubMedCrossRefGoogle Scholar
  62. Shuto T, Furuta T, Oba M, Xu H, Li J D, Cheung J, Gruenert D C, Uehara A, Suico M A, Okiyoneda T, Kai H (2006). Promoter hypomethylation of Toll-like receptor-2 gene is associated with increased proinflammatory response toward bacterial peptidoglycan in cystic fibrosis bronchial epithelial cells. FASEB J, 20(6): 782–784PubMedGoogle Scholar
  63. Smyth M J, Dunn G P, Schreiber R D (2006). Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol, 90: 1–50PubMedCrossRefGoogle Scholar
  64. Takahashi H, Ogata H, Nishigaki R, Broide D H, Karin M (2010). Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell, 17(1): 89–97PubMedCrossRefGoogle Scholar
  65. Thanos D, Maniatis T (1995). Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell, 83(7): 1091–1100PubMedCrossRefGoogle Scholar
  66. Treisman R (1986). Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell, 46 (4): 567–574PubMedCrossRefGoogle Scholar
  67. Uysal H, Bockermann R, Nandakumar K S, Sehnert B, Bajtner E, Engström A, Serre G, Burkhardt H, Thunnissen M M, Holmdahl R (2009). Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis. J Exp Med, 206(2): 449–462PubMedCrossRefGoogle Scholar
  68. Vallabhapurapu S, Karin M (2009). Regulation and function of NFkappaB transcription factors in the immune system. Annu Rev Immunol, 27(1): 693–733PubMedCrossRefGoogle Scholar
  69. Weinmann A S, Plevy S E, Smale S T (1999). Rapid and selective remodeling of a positioned nucleosome during the induction of IL-12 p40 transcription. Immunity, 11(6): 665–675PubMedCrossRefGoogle Scholar
  70. Weintraub H, Groudine M (1976). Chromosomal subunits in active genes have an altered conformation. Science, 193(4256): 848–856PubMedCrossRefGoogle Scholar
  71. Worm J, Stenvang J, Petri A, Frederiksen K S, Obad S, Elmén J, Hedtjärn M, Straarup E M, Hansen J B, Kauppinen S (2009). Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF. Nucleic Acids Res, 37(17): 5784–5792PubMedCrossRefGoogle Scholar
  72. Wu C, Bingham P M, Livak K J, Holmgren R, Elgin S C (1979). The chromatin structure of specific genes: I. Evidence for higher order domains of defined DNA sequence. Cell, 16(4): 797–806PubMedCrossRefGoogle Scholar
  73. Zhao K, Wang W, Rando O J, Xue Y, Swiderek K, Kuo A, Crabtree G R (1998). Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling. Cell, 95(5): 625–636PubMedCrossRefGoogle Scholar
  74. Zong W X, Thompson C B (2006). Necrotic death as a cell fate. Genes Dev, 20(1): 1–15PubMedCrossRefGoogle Scholar

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© Higher Education Press and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Centre for Inflammatory Diseases, Monash Medical CentreMonash University Department of MedicineClaytonAustralia

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