IL-1F5, -F6, -F8, and -F9: a Novel IL-1 Family Signaling System That is Active in Psoriasis and Promotes Keratinocyte Antimicrobial Peptide Expression

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2011 Jan 19

PMID 21242515

Citations 125

Authors

Andrew Johnston

Xianying Xing

Andrew M Guzman

Marybeth Riblett

Candace M Loyd

Nicole L Ward

Christian Wohn

Errol P Prens

Frank Wang

Lisa E Maier

Sewon Kang

John J Voorhees

James T Elder

Johann E Gudjonsson

Affiliations

Soon will be listed here.

Abstract

IL-1F6, IL-1F8, and IL-1F9 and the IL-1R6(RP2) receptor antagonist IL-1F5 constitute a novel IL-1 signaling system that is poorly characterized in skin. To further characterize these cytokines in healthy and inflamed skin, we studied their expression in healthy control, uninvolved psoriasis, and psoriasis plaque skin using quantitative RT-PCR and immunohistochemistry. Expression of IL-1F5, -1F6, -1F8, and -1F9 were increased 2 to 3 orders of magnitude in psoriasis plaque versus uninvolved psoriasis skin, which was supported immunohistologically. Moreover, treatment of psoriasis with etanercept led to significantly decreased IL-1F5, -1F6, -1F8, and -1F9 mRNAs, concomitant with clinical improvement. Similarly increased expression of IL-1F5, -1F6, -1F8, and -1F9 was seen in the involved skin of two mouse models of psoriasis. Suggestive of their importance in inflamed epithelia, IL-1α and TNF-α induced IL-1F5, -1F6, -1F8, and -1F9 transcript expression by normal human keratinocytes. Microarray analysis revealed that these cytokines induce the expression of antimicrobial peptides and matrix metalloproteinases by reconstituted human epidermis. In particular, IL-1F8 increased mRNA expression of human β-defensin (HBD)-2, HBD-3, and CAMP and protein secretion of HBD-2 and HBD-3. Collectively, our data suggest important roles for these novel cytokines in inflammatory skin diseases and identify these peptides as potential targets for antipsoriatic therapies.

Citing Articles

The Contribution of the Skin Microbiome to Psoriasis Pathogenesis and Its Implications for Therapeutic Strategies.

Radaschin D, Tatu A, Iancu A, Beiu C, Popa L Medicina (Kaunas). 2024; 60(10).

PMID: 39459406 PMC: 11509136. DOI: 10.3390/medicina60101619.

The Immunology of Psoriasis-Current Concepts in Pathogenesis.

Sieminska I, Pieniawska M, Grzywa T Clin Rev Allergy Immunol. 2024; 66(2):164-191.

PMID: 38642273 PMC: 11193704. DOI: 10.1007/s12016-024-08991-7.

Signaling pathways and targeted therapies for psoriasis.

Guo J, Zhang H, Lin W, Lu L, Su J, Chen X Signal Transduct Target Ther. 2023; 8(1):437.

PMID: 38008779 PMC: 10679229. DOI: 10.1038/s41392-023-01655-6.

Regulatory Mechanism of the IL-33-IL-37 Axis via Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis.

Tsuji G, Yamamura K, Kawamura K, Kido-Nakahara M, Ito T, Nakahara T Int J Mol Sci. 2023; 24(19).

PMID: 37834081 PMC: 10572928. DOI: 10.3390/ijms241914633.

Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin.

Xiao Q, Mears J, Nathan A, Ishigaki K, Baglaenko Y, Lim N Nat Commun. 2023; 14(1):6268.

PMID: 37805522 PMC: 10560299. DOI: 10.1038/s41467-023-41984-2.

References

Barton J, Herbst R, Bosisio D, Higgins L, Nicklin M . A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities. Eur J Immunol. 2000; 30(11):3299-308. DOI: 10.1002/1521-4141(200011)30:11<3299::AID-IMMU3299>3.0.CO;2-S. View

Stander M, Naumann U, Wick W, Weller M . Transforming growth factor-beta and p-21: multiple molecular targets of decorin-mediated suppression of neoplastic growth. Cell Tissue Res. 1999; 296(2):221-7. DOI: 10.1007/s004410051283. View

Cooper K, Hammerberg C, Baadsgaard O, Elder J, Chan L, Sauder D . IL-1 activity is reduced in psoriatic skin. Decreased IL-1 alpha and increased nonfunctional IL-1 beta. J Immunol. 1990; 144(12):4593-603. View

Gottlieb A, Chamian F, Masud S, Cardinale I, Abello M, Lowes M . TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol. 2005; 175(4):2721-9. DOI: 10.4049/jimmunol.175.4.2721. View

Kumar S, McDonnell P, Lehr R, Tierney L, Tzimas M, Griswold D . Identification and initial characterization of four novel members of the interleukin-1 family. J Biol Chem. 2000; 275(14):10308-14. DOI: 10.1074/jbc.275.14.10308. View

Schneider M, Antsiferova M, Feldmeyer L, Dahlhoff M, Bugnon P, Hasse S . Betacellulin regulates hair follicle development and hair cycle induction and enhances angiogenesis in wounded skin. J Invest Dermatol. 2007; 128(5):1256-65. DOI: 10.1038/sj.jid.5701135. View

Towne J, Garka K, Renshaw B, Virca G, Sims J . Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J Biol Chem. 2004; 279(14):13677-88. DOI: 10.1074/jbc.M400117200. View

Cordiali-Fei P, Trento E, DAgosto G, Bordignon V, Mussi A, Ardigo M . Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-alpha. J Autoimmune Dis. 2006; 3:5. PMC: 1601955. DOI: 10.1186/1740-2557-3-5. View

Veldhoen M, Hocking R, Atkins C, Locksley R, Stockinger B . TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006; 24(2):179-89. DOI: 10.1016/j.immuni.2006.01.001. View

10.

Smithgall M, Comeau M, Yoon B, Kaufman D, Armitage R, Smith D . IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol. 2008; 20(8):1019-30. DOI: 10.1093/intimm/dxn060. View

11.

Magne D, Palmer G, Barton J, Mezin F, Talabot-Ayer D, Bas S . The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes. Arthritis Res Ther. 2006; 8(3):R80. PMC: 1526623. DOI: 10.1186/ar1946. View

12.

Blumberg H, Dinh H, Trueblood E, Pretorius J, Kugler D, Weng N . Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med. 2007; 204(11):2603-14. PMC: 2118475. DOI: 10.1084/jem.20070157. View

13.

Pan G, Risser P, Mao W, Baldwin D, Zhong A, Filvaroff E . IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL-1Rrp. Cytokine. 2001; 13(1):1-7. DOI: 10.1006/cyto.2000.0799. View

14.

Lin H, Ho A, Zhang J, Pace A, Hansen D, Schweighofer K . Cloning and characterization of IL-1HY2, a novel interleukin-1 family member. J Biol Chem. 2001; 276(23):20597-602. DOI: 10.1074/jbc.M010095200. View

15.

Blumberg H, Dinh H, Dean Jr C, Trueblood E, Bailey K, Shows D . IL-1RL2 and its ligands contribute to the cytokine network in psoriasis. J Immunol. 2010; 185(7):4354-62. DOI: 10.4049/jimmunol.1000313. View

16.

Mease P, GOFFE B, Metz J, VanderStoep A, Finck B, Burge D . Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet. 2000; 356(9227):385-90. DOI: 10.1016/S0140-6736(00)02530-7. View

17.

Sims J, Nicklin M, Bazan J, Barton J, Busfield S, Ford J . A new nomenclature for IL-1-family genes. Trends Immunol. 2001; 22(10):536-7. DOI: 10.1016/s1471-4906(01)02040-3. View

18.

Luger T, Stadler B, Luger B, Mathieson B, Mage M, Schmidt J . Murine epidermal cell-derived thymocyte-activating factor resembles murine interleukin 1. J Immunol. 1982; 128(5):2147-52. View

19.

Gudjonsson J, Johnston A, Stoll S, Riblett M, Xing X, Kochkodan J . Evidence for altered Wnt signaling in psoriatic skin. J Invest Dermatol. 2010; 130(7):1849-59. PMC: 2886156. DOI: 10.1038/jid.2010.67. View

20.

Irizarry R, Bolstad B, Collin F, Cope L, Hobbs B, Speed T . Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res. 2003; 31(4):e15. PMC: 150247. DOI: 10.1093/nar/gng015. View