IL9

IL9
Identifikatori
Aliasi	IL9
Vanjski ID-jevi	OMIM: 146931 MGI: 96563 HomoloGene: 492 GeneCards: IL9
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	135,895,841 bp
Lokacija gena (miš)
Hrom.	Hromosom 13 (miš)
Kraj	56,630,059 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• interleukin-9 receptor binding; • cytokine activity; • growth factor activity; • GO:0005145 cytokine receptor binding;
Ćelijska komponenta	• extracellular region; • Vanćelijsko;
Biološki proces	• positive regulation of cell growth; • inflammatory response; • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor; • positive regulation of cell population proliferation; • regulation of signaling receptor activity; • interleukin-9-mediated signaling pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	3578
	16198
	ENSG00000145839
	ENSMUSG00000021538
	P15248
	P15247
	NM_000590
	NM_008373
	NP_000581
	NP_032399
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Interleukin 9, znan i kao IL-9, je plejotropni citokin (ćelijska signalna molekula) grupe interleukina.^[5] IL-9 proizvode različite ćelije kao što su mast-ćelije, NKT ćelije, Th2, Th17,Treg, ILC2 i Th9 ćelije u različitim količinama. Među njima, Th9-ćelije smatraju se glavnim CD4+ T-ćelije koje proizvode IL-9.^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 144 aminokiseline, a molekulska težina 15.909 Da.^[5]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MLLAMVLTSA	LLLCSVAGQG	CPTLAGILDI	NFLINKMQED	PASKCHCSAN
VTSCLCLGIP	SDNCTRPCFS	ERLSQMTNTT	MQTRYPLIFS	RVKKSVEVLK
NNKCPYFSCE	QPCNQTTAGN	ALTFLKSLLE	IFQKEKMRGM	RGKI

Struktura proteina

Ljudski IL-9 proteinSKA sekvenca sadrži 144 ostatka sa tipskim signalnim peptidom od 18 aminokiselina. Također postoji ima devet cisteina u zrelim polipeptidima i četiri mjestA N-vezane glikozilacije. Smatra se da je IL-9 evolucijski srodan IL-7.^[7] Međutim, sada se zna da je IL-9 bliži IL-2 i IL-15 nego IL-7,^[8] na nivou i tercijarne i aminokiselinske sekvence.

Funkcije

Il-9 je citokin koga luče CD4+ ćelije pomoćnice koji djeluje kao regulator raznih hematopoetskih ćelija.^[9] Ovaj citokin stimulira proliferaciju ćelija i sprečava apoptoze. Funkcioniše preko receptora interleukina-9 (IL9R), koji aktivira različite proteine pretvarača signala i aktivatora (STAT), STAT1, STAT3 i STAT5 i tako povezuje ovaj citokin s različitim biološkim procesima. Gen koji kodira ovaj citokin je identificiran kao gen kandidat za uzrokovanje astme. Genetičke studije na mišjem modelu astme pokazale su da je ovaj citokin odlučujući faktor u patogenezi bronhijske hiperreaktivnosti.^[5]

Interleukin-9 je također pokazao da inhibira rast melanoma kod miševa.^[10]

Osim toga, izaziva umnožavanje krvnih neoplazija i Hodgkinovog limfoma kod ljudi, ali IL-9 također ima antitumorska svojstva kod solidnih tumora, naprimjer melanoma.^[6]

Lokacija gena

Ljudski IL-9 gen je lociran na dugm kraku (q) ljudskog hromosoma 5 na pojasu 5q31-32, regije koja se ne nalazi kod određenog broja pacijenata sa stečenom sidromom hromosomske delecije 5q.^[11]

Proizvodnja

Interleukin 33 (IL-33) inducira ekspresiju i lučenje IL-9 u T-ćelijaama, što je potvrđeno rezultatima dobijenim na miševima upotrebom ljudsog in vitro sistema.^[12] Dok izvještaj drugih potvrđuje da je TGF-β bitan faktor za indukciju IL-9.^[13] Po prvi put (Lars Blom, Britta C. Poulsen, Bettina M. Jensen, Anker Hansen i Lars K. Poulsen objavili su časopis na onlajn mreži 6. jula 2011.), ukazujući da TGF-β može biti važan za proizvodnju IL-9, ali to nije samo definitivan zahtjev za indukciju IL-9, budući da kulture sa IL-33 bez TGF-β značajno povećavaju lučenje IL-9, što ukazuje na važnu ulogu IL-33, iako da efekat nije bio značajan na nivou gena.^[14]

Receptor nterleukina-9

IL-9 ima različite direktne i indirektne efekte na više tipova ćelija koji utiču na razvoj imunosti i upale.

Ekspresija IL-9

Analiza ekspresije IL-9 u različitim tipovima tumora kao što su anaplazijski limfom velikih ćelija (LCAL) i Hodgkinova bolest (HD) pomoću Northern blot analiza i in situ hibridizacija pokazala je da IL-9 nije uključen kao autokrini faktor rasta u patogenezama većine B i T-ćelijskih limfoma, ali može imati udio u HD i LCAL autokrinom rastu.

Dalje istraživanje bi se moglo obaviti kako bi se zaključila još jedna vjerovatnoća, da bi in vivo prekomerna ekspresija IL-9 mogla pokazati jedinstvene simptome povezane sa eozinofilijom koji su nedavno prijavljeni za Interleukin 5 pozitivne slučajeve HD.^[15]

Utvrđeno je da je IL-9 prvi fiziološki stimulus koji pokreće ekspresiju BCL3 u T– i mast-ćelijama, analizom urađenom na mišu.^[16]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000145839 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021538 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "Entrez Gene: IL9 interleukin 9".
^ ^a ^b Rojas-Zuleta WG, Sanchez E (2017). "IL-9: Function, Sources, and Detection". Th9 Cells. Methods in Molecular Biology. 1585. str. 21–35. doi:10.1007/978-1-4939-6877-0_2. hdl:10161/14730. ISBN 978-1-4939-6876-3. PMID 28477184.
^ Boulay, J. L.; Paul, W. E. (1. 9. 1993). "Hematopoietin sub-family classification based on size, gene organization and sequence homology". Current Biology. 3 (9): 573–581. doi:10.1016/0960-9822(93)90002-6. ISSN 0960-9822. PMID 15335670. S2CID 42479456.
^ Reche, Pedro A. (1. 2. 2019). "The tertiary structure of γc cytokines dictates receptor sharing". Cytokine. 116: 161–168. doi:10.1016/j.cyto.2019.01.007. ISSN 1096-0023. PMID 30716660. S2CID 73449371.
^ Perumal NB, Kaplan MH (2011). "Regulating IL9 transcription in T helper cells". Trends in Immunology. 32 (4): 146–50. doi:10.1016/j.it.2011.01.006. PMC 3070825. PMID 21371941.
^ Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS (august 2012). "Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells". Nature Medicine. 18 (8): 1248–53. doi:10.1038/nm.2856. PMC 3518666. PMID 22772464. Sažetak – medicalxpress.com.
^ Kelleher K, Bean K, Clark SC, Leung WY, Yang-Feng TL, Chen JW, Lin PF, Luo W, Yang YC (1991). "Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells" (PDF). Blood. 77 (7): 1436–41. doi:10.1182/blood.V77.7.1436.1436. PMID 1901233.
^ Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK (februar 2008). "IL-33, a potent inducer of adaptive immunity to intestinal nematodes". Journal of Immunology. 180 (4): 2443–9. doi:10.4049/jimmunol.180.4.2443. PMID 18250453.
^ Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA (juli 2010). "TGF-beta induces IL-9 production from human Th17 cells". Journal of Immunology. 185 (1): 46–54. doi:10.4049/jimmunol.1000356. PMC 2936106. PMID 20498357.
^ Blom L, Poulsen BC, Jensen BM, Hansen A, Poulsen LK (6. 7. 2011). "IL-33 induces IL-9 production in human CD4+ T cells and basophils". PLOS ONE. 6 (7): e21695. doi:10.1371/journal.pone.0021695. PMC 3130774. PMID 21765905.
^ Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, Van Snick J (1991). "Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma". Blood. 78 (5): 1311–7. doi:10.1182/blood.V78.5.1311.1311. PMID 1908723.
^ Richard M, Louahed J, Demoulin JB, Renauld JC (1999). "Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction". Blood. 93 (12): 4318–27. doi:10.1182/blood.V93.12.4318. PMID 10361130.

Dopunska literatura

Renauld JC, Houssiau F, Louahed J, Vink A, Van Snick J, Uyttenhove C (1993). "Interleukin-9". Advances in Immunology Volume 54. Advances in Immunology. 54. str. 79–97. doi:10.1016/S0065-2776(08)60533-7. ISBN 978-0-12-022454-8. PMID 8379467.
Knoops L, Renauld JC (decembar 2004). "IL-9 and its receptor: from signal transduction to tumorigenesis". Growth Factors. 22 (4): 207–15. doi:10.1080/08977190410001720879. PMID 15621723. S2CID 40523692.
Modi WS, Pollock DD, Mock BA, Banner C, Renauld JC, Van Snick J (1991). "Regional localization of the human glutaminase (GLS) and interleukin-9 (IL9) genes by in situ hybridization". Cytogenetics and Cell Genetics. 57 (2–3): 114–6. doi:10.1159/000133126. PMID 1680606.
Kelleher K, Bean K, Clark SC, Leung WY, Yang-Feng TL, Chen JW, Lin PF, Luo W, Yang YC (april 1991). "Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells". Blood. 77 (7): 1436–41. doi:10.1182/blood.V77.7.1436.1436. PMID 1901233.
Holbrook ST, Ohls RK, Schibler KR, Yang YC, Christensen RD (maj 1991). "Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors". Blood. 77 (10): 2129–34. doi:10.1182/blood.V77.10.2129.2129. PMID 1903074.
Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, Van Snick J (septembar 1991). "Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma". Blood. 78 (5): 1311–7. doi:10.1182/blood.V78.5.1311.1311. PMID 1908723.
Renauld JC, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J (juni 1990). "Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene". Journal of Immunology. 144 (11): 4235–41. PMID 1971295.
Renauld JC, Goethals A, Houssiau F, Van Roost E, Van Snick J (januar 1990). "Cloning and expression of a cDNA for the human homolog of mouse T cell and mast cell growth factor P40". Cytokine. 2 (1): 9–12. doi:10.1016/1043-4666(90)90037-T. hdl:2078.1/11464. PMID 2129501.
Yang YC, Ricciardi S, Ciarletta A, Calvetti J, Kelleher K, Clark SC (novembar 1989). "Expression cloning of cDNA encoding a novel human hematopoietic growth factor: human homologue of murine T-cell growth factor P40". Blood. 74 (6): 1880–4. doi:10.1182/blood.V74.6.1880.1880. PMID 2508790.
Yin T, Keller SR, Quelle FW, Witthuhn BA, Tsang ML, Lienhard GE, Ihle JN, Yang YC (septembar 1995). "Interleukin-9 induces tyrosine phosphorylation of insulin receptor substrate-1 via JAK tyrosine kinases". The Journal of Biological Chemistry. 270 (35): 20497–502. doi:10.1074/jbc.270.35.20497. PMID 7544789.
Postma DS, Bleecker ER, Amelung PJ, Holroyd KJ, Xu J, Panhuysen CI, Meyers DA, Levitt RC (oktobar 1995). "Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy". The New England Journal of Medicine. 333 (14): 894–900. doi:10.1056/NEJM199510053331402. PMID 7666875.
Le Beau MM, Espinosa R, Neuman WL, Stock W, Roulston D, Larson RA, Keinanen M, Westbrook CA (juni 1993). "Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases". Proceedings of the National Academy of Sciences of the United States of America. 90 (12): 5484–8. doi:10.1073/pnas.90.12.5484. PMC 46745. PMID 8516290.
Demoulin JB, Uyttenhove C, Van Roost E, DeLestré B, Donckers D, Van Snick J, Renauld JC (septembar 1996). "A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9". Molecular and Cellular Biology. 16 (9): 4710–6. doi:10.1128/mcb.16.9.4710. PMC 231471. PMID 8756628.
Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, Sullivan CD, Grasso L, Zhang LY, Messler CJ, Zhou T, Kleeberger SR, Buetow KH, Levitt RC (novembar 1997). "Interleukin 9: a candidate gene for asthma". Proceedings of the National Academy of Sciences of the United States of America. 94 (24): 13175–80. doi:10.1073/pnas.94.24.13175. PMC 24282. PMID 9371819.
Demoulin JB, Van Roost E, Stevens M, Groner B, Renauld JC (septembar 1999). "Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9". The Journal of Biological Chemistry. 274 (36): 25855–61. doi:10.1074/jbc.274.36.25855. PMID 10464327.
Lejeune D, Demoulin JB, Renauld JC (januar 2001). "Interleukin 9 induces expression of three cytokine signal inhibitors: cytokine-inducible SH2-containing protein, suppressor of cytokine signalling (SOCS)-2 and SOCS-3, but only SOCS-3 overexpression suppresses interleukin 9 signalling". The Biochemical Journal. 353 (Pt 1): 109–116. doi:10.1042/0264-6021:3530109. PMC 1221548. PMID 11115404.
Little FF, Cruikshank WW, Center DM (septembar 2001). "Il-9 stimulates release of chemotactic factors from human bronchial epithelial cells". American Journal of Respiratory Cell and Molecular Biology. 25 (3): 347–52. doi:10.1165/ajrcmb.25.3.4349. PMID 11588013.
Toda M, Tulic MK, Levitt RC, Hamid Q (februar 2002). "A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma". The Journal of Allergy and Clinical Immunology. 109 (2): 246–50. doi:10.1067/mai.2002.121555. PMID 11842292.
Pilette C, Ouadrhiri Y, Van Snick J, Renauld JC, Staquet P, Vaerman JP, Sibille Y (april 2002). "IL-9 inhibits oxidative burst and TNF-alpha release in lipopolysaccharide-stimulated human monocytes through TGF-beta". Journal of Immunology. 168 (8): 4103–11. doi:10.4049/jimmunol.168.8.4103. PMID 11937570.

Vanjski linkovi

Šablon:Interleukini Šablon:Modulatoeri interleukinskog receptora

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000145839 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021538 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: IL9 interleukin 9".

[ReferenceA-6] Rojas-Zuleta WG, Sanchez E (2017). "IL-9: Function, Sources, and Detection". Th9 Cells. Methods in Molecular Biology. 1585. str. 21–35. doi:10.1007/978-1-4939-6877-0_2. hdl:10161/14730. ISBN 978-1-4939-6876-3. PMID 28477184.

[7] Boulay, J. L.; Paul, W. E. (1. 9. 1993). "Hematopoietin sub-family classification based on size, gene organization and sequence homology". Current Biology. 3 (9): 573–581. doi:10.1016/0960-9822(93)90002-6. ISSN 0960-9822. PMID 15335670. S2CID 42479456.

[8] Reche, Pedro A. (1. 2. 2019). "The tertiary structure of γc cytokines dictates receptor sharing". Cytokine. 116: 161–168. doi:10.1016/j.cyto.2019.01.007. ISSN 1096-0023. PMID 30716660. S2CID 73449371.

[pmid21371941-9] Perumal NB, Kaplan MH (2011). "Regulating IL9 transcription in T helper cells". Trends in Immunology. 32 (4): 146–50. doi:10.1016/j.it.2011.01.006. PMC 3070825. PMID 21371941.

[pmid22772464-10] Purwar R, Schlapbach C, Xiao S, Kang HS, Elyaman W, Jiang X, Jetten AM, Khoury SJ, Fuhlbrigge RC, Kuchroo VK, Clark RA, Kupper TS (august 2012). "Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells". Nature Medicine. 18 (8): 1248–53. doi:10.1038/nm.2856. PMC 3518666. PMID 22772464. Sažetak – medicalxpress.com.

[pmid1901233-11] Kelleher K, Bean K, Clark SC, Leung WY, Yang-Feng TL, Chen JW, Lin PF, Luo W, Yang YC (1991). "Human interleukin-9: genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells" (PDF). Blood. 77 (7): 1436–41. doi:10.1182/blood.V77.7.1436.1436. PMID 1901233.

[12] Humphreys NE, Xu D, Hepworth MR, Liew FY, Grencis RK (februar 2008). "IL-33, a potent inducer of adaptive immunity to intestinal nematodes". Journal of Immunology. 180 (4): 2443–9. doi:10.4049/jimmunol.180.4.2443. PMID 18250453.

[13] Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA (juli 2010). "TGF-beta induces IL-9 production from human Th17 cells". Journal of Immunology. 185 (1): 46–54. doi:10.4049/jimmunol.1000356. PMC 2936106. PMID 20498357.

[14] Blom L, Poulsen BC, Jensen BM, Hansen A, Poulsen LK (6. 7. 2011). "IL-33 induces IL-9 production in human CD4+ T cells and basophils". PLOS ONE. 6 (7): e21695. doi:10.1371/journal.pone.0021695. PMC 3130774. PMID 21765905.

[pmid1908723-15] Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, Van Snick J (1991). "Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma". Blood. 78 (5): 1311–7. doi:10.1182/blood.V78.5.1311.1311. PMID 1908723.

[pmid10361130-16] Richard M, Louahed J, Demoulin JB, Renauld JC (1999). "Interleukin-9 regulates NF-kappaB activity through BCL3 gene induction". Blood. 93 (12): 4318–27. doi:10.1182/blood.V93.12.4318. PMID 10361130.

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