同: interleukin-8

同: interleukin-8

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/07 01:04:12」(JST)

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Interleukin 8 (IL-8) or CXCL8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells^[1] and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies.^[2]^[3] In humans, the interleukin-8 protein is encoded by the IL8 gene.^[4]

There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Toll-like receptors are the receptors of the innate immune system. These receptors recognize antigen patterns (like LPS in gram negative bacteria). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response.

Function

IL-8, also known as neutrophil chemotactic factor, has two primary functions. It induces chemotaxis in target cells, primarily neutrophils but also other granulocytes, causing them to migrate toward the site of infection. IL-8 also induces phagocytosis once they have arrived. IL-8 is also known to be a potent promoter of angiogenesis. In target cells, IL-8 induces a series of physiological responses required for migration and phagocytosis, such as increases in intracellular Ca²⁺, exocytosis (e.g. histamine release), and the respiratory burst.

IL-8 can be secreted by any cells with toll-like receptors that are involved in the innate immune response. Usually, it is the macrophages that see an antigen first, and thus are the first cells to release IL-8 to recruit other cells. Both monomer and homodimer forms of IL-8 have been reported to be potent inducers of the chemokine receptors CXCR1 and CXCR2. The homodimer is more potent, but methylation of Leu25 can block the activity of homodimers.

IL-8 is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection.{fact}

IL-8 is a member of the CXC chemokine family. The genes encoding this and the other ten members of the CXC chemokine family form a cluster in a region mapped to chromosome 4q.^[4]^[5]

Target cells

While neutrophil granulocytes are the primary target cells of IL-8, there are a relatively wide range of cells (endothelial cells, macrophages, mast cells, and keratinocytes) that respond to this chemokine. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proven in Tetrahymena pyriformis, which suggests a phylogenetically well-conserved structure and function for this chemokine.^[6]

Clinical significance

Interleukin-8 is often associated with inflammation. As an example, it has been cited as a proinflammatory mediator in gingivitis^[7] and psoriasis.[2]. Interleukin-8 secretion is increased by oxidant stress, which thereby cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation.^[8] IL-8 was shown to be associated with obesity.^[9]

If a pregnant mother has high levels of interleukin-8, there is an increased risk of schizophrenia in her offspring.^[10] High levels of Interleukin 8 have been shown to reduce the likelihood of positive responses to antipsychotic medication in schizophrenia.^[11]

Nomenclature

IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies,.^[12] Its approved HUGO gene symbol is CXCL8.

Regulation of Expression

The expression of IL-8 is negatively regulated by a number of mechanisms. MiRNA-146a/b-5p indirectly represses IL-8 expression by silencing the expression of IRAK1.^[13] Additionally, the 3'UTR of IL-8 contains a A/U-rich element that makes it extremely unstable under certain conditions. IL-8 expression is also regulated by the transcription factor NF-κB.^[14] NF-κB regulation represents a novel anti-IL-8 therapy for use in inflammatory diseases such as cystic fibrosis.

References

^ Hedges JC, Singer CA, Gerthoffer WT (July 2000). "Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes". Am. J. Respir. Cell Mol. Biol. 23 (1): 86–94. doi:10.1165/ajrcmb.23.1.4014. PMID 10873157.
^ Wolff B, Burns AR, Middleton J, Rot A (November 1998). "Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies". J. Exp. Med. 188 (9): 1757–62. doi:10.1084/jem.188.9.1757. PMC 2212526. PMID 9802987.
^ Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G (November 1998). "Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells". J. Exp. Med. 188 (9): 1751–6. doi:10.1084/jem.188.9.1751. PMC 2212514. PMID 9802986.
^ ^a ^b Modi WS, Dean M, Seuanez HN, Mukaida N, Matsushima K, O'Brien SJ (January 1990). "Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily". Hum. Genet. 84 (2): 185–7. doi:10.1007/BF00208938. PMID 1967588.
^ "Entrez Gene: IL8 interleukin 8".
^ Köhidai L, Csaba G (July 1998). "Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF-alpha) in the unicellular Tetrahymena pyriformis". Cytokine 10 (7): 481–6. doi:10.1006/cyto.1997.0328. PMID 9702410.
^ Haake, SK, Huang, GTJ: Molecular Biology of the host-Microbe Interaction in Periodontal Diseases (Selected Topics). In Newman, Takei, Carranza, editors: Clinical Periodontology, 9th Edition. Philadelphia: W.B.Saunders Co. 2002. page 162.
^ Vlahopoulos S, Boldogh I, Casola A, Brasier AR (September 1999). "Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation". Blood 94 (6): 1878–89. PMID 10477716.
^ Sharabiani, M.T.; Vermeulen R, Scoccianti C, Hosnijeh FS, Minelli L, Sacerdote C, Palli D, Krogh V, Tumino R, Chiodini P, Panico S, Vineis P. (May 2011). "Immunologic profile of excessive body weight". Biomarkers 16 (3): 243–51. doi:10.3109/1354750X.2010.547948. PMID 21506696. Cite uses deprecated parameters (help)
^ Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES (May 2004). "Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring". Am J Psychiatry 161 (5): 889–95. doi:10.1176/appi.ajp.161.5.889. PMID 15121655.
^ Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (July 2004). "Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia". J Clin Psychiatry 65 (7): 940–7. doi:10.4088/JCP.v65n0710. PMID 15291683.
^ Bacon K, Baggiolini M, Broxmeyer H, Horuk R, Lindley I, Mantovani A, Maysushima K, Murphy P, Nomiyama H, Oppenheim J, Rot A, Schall T, Tsang M, Thorpe R, Van Damme J, Wadhwa M, Yoshie O, Zlotnik A, Zoon K (October 2002). "Chemokine/chemokine receptor nomenclature". J. Interferon Cytokine Res. 22 (10): 1067–8. doi:10.1089/107999002760624305. PMID 12433287.
^ Bhaumik D, Scott GK, Schokrpur S, Patil CK, Orjalo AV, Rodier F, Lithgow GJ, Campisi J (April 2009). "MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8". Aging (Albany NY) 1 (4): 402–11. PMC 2818025. PMID 20148189.
^ Rottner, Mathilde; Freyssinet, Martinez (2009). "Mechanisms of the noxious inflammatory cycle in cystic fibrosis". Respiratory Research 10: 1–11. doi:10.1186/1465-9921-10-23.

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4. 成人における刺激性接触皮膚炎 irritant contact dermatitis in adults
5. エルドハイム・チェスター病 erdheim chester disease

English Journal

Early-Pregnancy Cytokines in Mothers to Children Developing Multiple, Persistent Islet Autoantibodies, Type 1 Diabetes, or Both Before 7 Years of Age.

Lindehammer SR, Fex M, Maziarz M, Hanson I, Maršál K, Lernmark A; on behalf of the Diabetes Prediction in Skåne (DiPiS) Study Group.SourceDepartment of Clinical Sciences, Unit of Diabetes and Celiac Disease, Skåne University Hospital SUS, University of Lund, Malmö, Sweden Department of Biostatistics, University of Washington, Seattle, WA, USA Department of Obstetrics and Gynecology, Clinical Sciences, Skåne University Hospital SUS, Lund, Sweden.
American journal of reproductive immunology (New York, N.Y. : 1989).Am J Reprod Immunol.2011 Dec;66(6):495-503. doi: 10.1111/j.1600-0897.2011.01057.x. Epub 2011 Aug 7.
Citation Lindehammer SR, Fex M, Maziarz M, Hanson I, Maršál K, Lernmark Å on behalf of the Diabetes Prediction in Skåne (DiPiS) Study Group. Early-pregnancy cytokines in mothers to children developing multiple, persistent islet autoantibodies, type 1 diabetes, or both before 7 years of age. Am
PMID 21819478

P2Y(6) receptor contributes to neutrophil recruitment to inflamed intestinal mucosa by increasing CXC chemokine ligand 8 expression in an AP-1-dependent manner in epithelial cells.

Grbic DM, Degagn E, Larrive JF, Bilodeau MS, Vinette V, Arguin G, Stankova J, Gendron FP.SourceDepartment of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Inflammatory bowel diseases.Inflamm Bowel Dis.2011 Nov 17. doi: 10.1002/ibd.21931. [Epub ahead of print]
BACKGROUND: Inflammatory bowel diseases are characterized by the presence of CXCL8 at the site of lesions resulting in neutrophil recruitment and loss of tissue functions. We report that P2Y(6) receptor activation stimulates CXCL8 expression and release by intestinal epithelial cells (IECs). In thi
PMID 22095787

Japanese Journal

PS-105-2 Gemcitabine耐性膵癌細胞株はCXCL8産生・分泌の充進により血管新生を促進する(PS-105 ポスターセッション(105)膵臓:基礎-2,第111回日本外科学会定期学術集会)

小出修司,松尾洋一,越智靖夫,原賢康,若杉健弘,高山悟,舟橋整,佐藤幹則,岡田祐二,桑原義之,竹山廣光
日本外科学会雑誌 112(臨時増刊号_1・2), 686, 2011-05-25
NAID 110008685040

SF-095-5 SIRSにおけるCXCL8の発現の意義とその受容体(CXCR1,CXCR2)を標的とした治療戦略(サージカルフォーラム(95)救急・外傷-2,第111回日本外科学会定期学術集会)

蒲原英伸,高橋将史,石河隆敏,境恵祐,廣佐古進,鷺島克之,木下順弘,馬場秀夫
日本外科学会雑誌 112(臨時増刊号_1・2), 455, 2011-05-25
NAID 110008684130

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「IL-8」

Chemokine (C-X-C motif) ligand 8
	; PDB rendering based on 1IL8.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1ICW, 1IKL, 1IKM, 1IL8, 1ILP, 1ILQ, 1QE6, 1ROD, 2IL8, 3IL8
Identifiers
Symbols	CXCL8 ; GCP-1; GCP1; IL8; LECT; LUCT; LYNAP; MDNCF; MONAP; NAF; NAP-1; NAP1
External IDs	OMIM: 146930 HomoloGene: 47937 ChEMBL: 2157 GeneCards: CXCL8 Gene
Gene ontology
Molecular function	• interleukin-8 receptor binding; • protein binding; • chemokine activity;
Cellular component	• extracellular region; • extracellular space;
Biological process	• angiogenesis; • response to molecule of bacterial origin; • cellular component movement; • chemotaxis; • inflammatory response; • immune response; • activation of signaling protein activity involved in unfolded protein response; • cell cycle arrest; • signal transduction; • G-protein coupled receptor signaling pathway; • negative regulation of cell proliferation; • calcium-mediated signaling; • regulation of cell adhesion; • neutrophil chemotaxis; • endoplasmic reticulum unfolded protein response; • receptor internalization; • response to endoplasmic reticulum stress; • intracellular signal transduction; • neutrophil activation; • cellular protein metabolic process; • cellular response to fibroblast growth factor stimulus; • regulation of single stranded viral RNA replication via double stranded DNA intermediate; • negative regulation of G-protein coupled receptor protein signaling pathway; • embryonic digestive tract development; • induction of positive chemotaxis; • cellular response to lipopolysaccharide; • cellular response to interleukin-1; • cellular response to tumor necrosis factor; • positive regulation of neutrophil chemotaxis;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: interleukin-8 IL-8
同: NAP-1
関: CXCL8

[pmid10873157-1] Hedges JC, Singer CA, Gerthoffer WT (July 2000). "Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes". Am. J. Respir. Cell Mol. Biol. 23 (1): 86–94. doi:10.1165/ajrcmb.23.1.4014. PMID 10873157.

[pmid9802987-2] Wolff B, Burns AR, Middleton J, Rot A (November 1998). "Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies". J. Exp. Med. 188 (9): 1757–62. doi:10.1084/jem.188.9.1757. PMC 2212526. PMID 9802987.

[pmid9802986-3] Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G (November 1998). "Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells". J. Exp. Med. 188 (9): 1751–6. doi:10.1084/jem.188.9.1751. PMC 2212514. PMID 9802986.

[pmid1967588-4] Modi WS, Dean M, Seuanez HN, Mukaida N, Matsushima K, O'Brien SJ (January 1990). "Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily". Hum. Genet. 84 (2): 185–7. doi:10.1007/BF00208938. PMID 1967588.

[5] "Entrez Gene: IL8 interleukin 8".

[pmid9702410-6] Köhidai L, Csaba G (July 1998). "Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF-alpha) in the unicellular Tetrahymena pyriformis". Cytokine 10 (7): 481–6. doi:10.1006/cyto.1997.0328. PMID 9702410.

[7] Haake, SK, Huang, GTJ: Molecular Biology of the host-Microbe Interaction in Periodontal Diseases (Selected Topics). In Newman, Takei, Carranza, editors: Clinical Periodontology, 9th Edition. Philadelphia: W.B.Saunders Co. 2002. page 162.

[pmid10477716-8] Vlahopoulos S, Boldogh I, Casola A, Brasier AR (September 1999). "Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation". Blood 94 (6): 1878–89. PMID 10477716.

[ImmunologicProfile-9] Sharabiani, M.T.; Vermeulen R, Scoccianti C, Hosnijeh FS, Minelli L, Sacerdote C, Palli D, Krogh V, Tumino R, Chiodini P, Panico S, Vineis P. (May 2011). "Immunologic profile of excessive body weight". Biomarkers 16 (3): 243–51. doi:10.3109/1354750X.2010.547948. PMID 21506696. Cite uses deprecated parameters (help)

[pmid15121655-10] Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES (May 2004). "Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring". Am J Psychiatry 161 (5): 889–95. doi:10.1176/appi.ajp.161.5.889. PMID 15121655.

[pmid15291683-11] Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (July 2004). "Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia". J Clin Psychiatry 65 (7): 940–7. doi:10.4088/JCP.v65n0710. PMID 15291683.

[pmid12433287-12] Bacon K, Baggiolini M, Broxmeyer H, Horuk R, Lindley I, Mantovani A, Maysushima K, Murphy P, Nomiyama H, Oppenheim J, Rot A, Schall T, Tsang M, Thorpe R, Van Damme J, Wadhwa M, Yoshie O, Zlotnik A, Zoon K (October 2002). "Chemokine/chemokine receptor nomenclature". J. Interferon Cytokine Res. 22 (10): 1067–8. doi:10.1089/107999002760624305. PMID 12433287.

[pmid20148189-13] Bhaumik D, Scott GK, Schokrpur S, Patil CK, Orjalo AV, Rodier F, Lithgow GJ, Campisi J (April 2009). "MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8". Aging (Albany NY) 1 (4): 402–11. PMC 2818025. PMID 20148189.

[14] Rottner, Mathilde; Freyssinet, Martinez (2009). "Mechanisms of the noxious inflammatory cycle in cystic fibrosis". Respiratory Research 10: 1–11. doi:10.1186/1465-9921-10-23.

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CXCL8