Skip to main content
Log in

An overview of inflammation: mechanism and consequences

  • Review
  • Published:
Frontiers in Biology

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • 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): 425–430

    Article  PubMed  CAS  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006). Pathogen recognition and innate immunity. Cell, 124(4): 783–801

    Article  PubMed  CAS  Google Scholar 

  • 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): 5246–5259

    Article  PubMed  CAS  Google Scholar 

  • Barnes P J (2009). Targeting the epigenome in the treatment of asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc, 6(8): 693–696

    Article  PubMed  CAS  Google Scholar 

  • Bayarsaihan D (2011). Epigenetic mechanisms in inflammation. J Dent Res, 90(1): 9–17

    Article  PubMed  CAS  Google Scholar 

  • 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): 1386–1392

    Article  PubMed  CAS  Google Scholar 

  • 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): 798–810

    Article  PubMed  CAS  Google Scholar 

  • 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): 843–851

    Article  PubMed  CAS  Google Scholar 

  • Carey MF, Peterson C L, Smale S T 2009. Transcriptional Regulation in Eukaryotes: Concepts, Strategies, and Techniques. New York: Cold Spring Harbor Laboratory Press

    Google Scholar 

  • 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): 53–60

    Article  PubMed  CAS  Google Scholar 

  • 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): 597–612

    Article  PubMed  CAS  Google Scholar 

  • de Martel C, Franceschi S (2009). Infections and cancer: established associations and new hypotheses. Crit Rev Oncol Hematol, 70(3): 183–194

    Article  PubMed  Google Scholar 

  • 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): 1083–1094

    Article  PubMed  Google Scholar 

  • de Visser K E, Eichten A, Coussens LM (2006). Paradoxical roles of the immune system during cancer development. Nat Rev Cancer, 6(1): 24–37

    Article  PubMed  Google Scholar 

  • 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): 494–499

    Article  PubMed  CAS  Google Scholar 

  • Garrett W S, Gordon J I, Glimcher L H (2010). Homeostasis and inflammation in the intestine. Cell, 140(6): 859–870

    Article  PubMed  CAS  Google Scholar 

  • 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): 225–260

    Article  PubMed  CAS  Google Scholar 

  • Glass C K, Saijo K, Winner B, Marchetto M C, Gage F H (2010). Mechanisms underlying inflammation in neurodegeneration. Cell, 140(6): 918–934

    Article  PubMed  CAS  Google Scholar 

  • Greenberg M E, Ziff E B (1984). Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature, 311(5985): 433–438

    Article  PubMed  CAS  Google Scholar 

  • Grivennikov S I, Greten F R, Karin M (2010). Immunity, inflammation, and cancer. Cell, 140(6): 883–899

    Article  PubMed  CAS  Google Scholar 

  • Hager G L, McNally J G, Misteli T (2009). Transcription dynamics. Mol Cell, 35(6): 741–753

    Article  PubMed  CAS  Google Scholar 

  • Hargreaves D C, Horng T, Medzhitov R (2009). Control of inducible gene expression by signal-dependent transcriptional elongation. Cell, 138(1): 129–145

    Article  PubMed  CAS  Google Scholar 

  • 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): 289–296

    PubMed  CAS  Google Scholar 

  • 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): 349–360

    Article  PubMed  CAS  Google Scholar 

  • Hotamisligil G S (2006). Inflammation and metabolic disorders. Nature, 444(7121): 860–867

    Article  PubMed  CAS  Google Scholar 

  • 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): 235–249

    Article  PubMed  CAS  Google Scholar 

  • Imbalzano A N, Kwon H, Green M R, Kingston R E (1994). Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature, 370(6489): 481–485

    Article  PubMed  CAS  Google Scholar 

  • 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): 595–602

    Article  PubMed  CAS  Google Scholar 

  • Kovesdi I, Reichel R, Nevins J R (1986). Identification of a cellular transcription factor involved in E1A trans-activation. Cell, 45(2): 219–228

    Article  PubMed  CAS  Google Scholar 

  • Kumar V, Carey M, Robbins S L 2003. Robbins Basic Pathology. 7th edition. New York: Saunders

    Google Scholar 

  • 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): 477–481

    Article  PubMed  CAS  Google Scholar 

  • 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): 1169–1174

    Article  PubMed  CAS  Google Scholar 

  • Lin W W, Karin M (2007). A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest, 117(5): 1175–1183

    Article  PubMed  CAS  Google Scholar 

  • 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): 15819–15824

    Article  PubMed  CAS  Google Scholar 

  • Locksley R M (2010). Asthma and allergic inflammation. Cell, 140(6): 777–783

    Article  PubMed  CAS  Google Scholar 

  • 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): 251–260

    Article  PubMed  CAS  Google Scholar 

  • 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): 977–990

    Article  PubMed  CAS  Google Scholar 

  • Majno G, Joris I 2004. Cells, Tissues, and Diseases. Second Edition. Oxford: Oxford University Press

    Google Scholar 

  • Mantovani A, Allavena P, Sica A, Balkwill F (2008). Cancer-related inflammation. Nature, 454(7203): 436–444

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov R (2007). Recognition of microorganisms and activation of the immune response. Nature, 449(7164): 819–826

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov R (2008). Origin and physiological roles of inflammation. Nature, 454(7203): 428–435

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov R (2010). Inflammation 2010: new adventures of an old flame. Cell, 140(6): 771–776

    Article  PubMed  CAS  Google Scholar 

  • 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): 175–178

    Article  PubMed  CAS  Google Scholar 

  • 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): 1133–1136

    Article  PubMed  CAS  Google Scholar 

  • 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): 1430–1440

    Article  PubMed  CAS  Google Scholar 

  • Okazaki I M, Kotani A, Honjo T (2007). Role of AID in tumorigenesis. Adv Immunol, 94: 245–273

    Article  PubMed  CAS  Google Scholar 

  • Ouyang W, Kolls J K, Zheng Y (2008). The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity, 28(4): 454–467

    Article  PubMed  CAS  Google Scholar 

  • 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): 4384–4393

    Article  PubMed  CAS  Google Scholar 

  • Panne D, Maniatis T, Harrison S C (2007). An atomic model of the interferon-beta enhanceosome. Cell, 129(6): 1111–1123

    Article  PubMed  CAS  Google Scholar 

  • Prywes R, Roeder R G (1986). Inducible binding of a factor to the c-fos enhancer. Cell, 47(5): 777–784

    Article  PubMed  CAS  Google Scholar 

  • 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): 114–128

    Article  PubMed  CAS  Google Scholar 

  • 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): 282–296

    Article  PubMed  CAS  Google Scholar 

  • 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): 298–304

    Article  PubMed  CAS  Google Scholar 

  • 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): 1084–1090

    Article  PubMed  CAS  Google Scholar 

  • 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): 546–558

    Article  PubMed  CAS  Google Scholar 

  • Saccani S, Natoli G (2002). Dynamic changes in histone H3 Lys 9 methylation occurring at tightly regulated inducible inflammatory genes. Genes Dev, 16(17): 2219–2224

    Article  PubMed  CAS  Google Scholar 

  • Saccani S, Pantano S, Natoli G (2001). Two waves of nuclear factor kappaB recruitment to target promoters. J Exp Med, 193(12): 1351–1359

    Article  PubMed  CAS  Google Scholar 

  • 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): 156–165

    Article  PubMed  CAS  Google Scholar 

  • Sen R, Baltimore D (1986). Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell, 47(6): 921–928

    Article  PubMed  CAS  Google Scholar 

  • Serhan C N, Savill J (2005). Resolution of inflammation: the beginning programs the end. Nat Immunol, 6(12): 1191–1197

    Article  PubMed  CAS  Google Scholar 

  • 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): 965–973

    Article  PubMed  CAS  Google Scholar 

  • 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): 782–784

    PubMed  CAS  Google Scholar 

  • 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: 1–50

    Article  PubMed  CAS  Google Scholar 

  • 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): 89–97

    Article  PubMed  CAS  Google Scholar 

  • Thanos D, Maniatis T (1995). Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell, 83(7): 1091–1100

    Article  PubMed  CAS  Google Scholar 

  • Treisman R (1986). Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell, 46 (4): 567–574

    Article  PubMed  CAS  Google Scholar 

  • 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): 449–462

    Article  PubMed  CAS  Google Scholar 

  • Vallabhapurapu S, Karin M (2009). Regulation and function of NFkappaB transcription factors in the immune system. Annu Rev Immunol, 27(1): 693–733

    Article  PubMed  CAS  Google Scholar 

  • 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): 665–675

    Article  PubMed  CAS  Google Scholar 

  • Weintraub H, Groudine M (1976). Chromosomal subunits in active genes have an altered conformation. Science, 193(4256): 848–856

    Article  PubMed  CAS  Google Scholar 

  • 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): 5784–5792

    Article  PubMed  CAS  Google Scholar 

  • 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): 797–806

    Article  PubMed  CAS  Google Scholar 

  • 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): 625–636

    Article  PubMed  CAS  Google Scholar 

  • Zong W X, Thompson C B (2006). Necrotic death as a cell fate. Genes Dev, 20(1): 1–15

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Afsar U. Ahmed.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahmed, A.U. An overview of inflammation: mechanism and consequences. Front. Biol. 6, 274–281 (2011). https://doi.org/10.1007/s11515-011-1123-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11515-011-1123-9

Keywords

Navigation