The Pro-inflammatory Cytokine IL-22 Up-regulates Keratin 17 Expression in Keratinocytes Via STAT3 and ERK1/2

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jul 19

PMID 22808266

Citations 36

Authors

Wei Zhang

Erle Dang

Xiaowei Shi

Liang Jin

Zhenzhen Feng

Lei Hu

Yan Wu

Gang Wang

Affiliations

Soon will be listed here.

Abstract

Background: To investigate the regulation of K17 expression by the pro-inflammatory cytokine IL-22 in keratinocytes and its important role in our previously hypothesized "K17/T cell/cytokine autoimmune loop" in psoriasis.

Materials And Methods: K17 expression was examined in the IL-22-treated keratinocytes by real-time quantitative PCR, ELISA, Western blot and Immunofluorescence. In addition, the signaling pathways involved in K17 regulation were investigated with related inhibitors and siRNAs. In addition, K17 expression was examined in the epidermis of IL-22-injected mouse skin.

Results: IL-22-induced K17 expression was confirmed in keratinocytes and the epidermis of IL-22-injected mouse skin at both mRNA and protein levels, which is an important complement to the autoimmune loop. We further investigated the regulatory mechanisms and found that both STAT3 and ERK1/2 were involved in the up-regulation of K17 expression induced by IL-22.

Conclusion: IL-22 up-regulates K17 expression in keratinocytes in a dose-dependent manner through STAT3- and ERK1/2-dependent mechanisms. These findings indicated that IL-22 was also involved in the K17/T cell/cytokine autoimmune loop and may play an important role in the progression of psoriasis.

Citing Articles

Effect of tumour necrotic factor-α, interleukin-17 and interleukin-22 on the expression of filaggerin-2 and hornerin: Analysis of a three-dimensional psoriatic skin model.

Makino T, Mizawa M, Takemoto K, Yamamoto S, Shimizu T Skin Health Dis. 2024; 4(6):e440.

PMID: 39624730 PMC: 11608895. DOI: 10.1002/ski2.440.

Keratins 6, 16, and 17 in Health and Disease: A Summary of Recent Findings.

Romashin D, Tolstova T, Varshaver A, Kozhin P, Rusanov A, Luzgina N Curr Issues Mol Biol. 2024; 46(8):8627-8641.

PMID: 39194725 PMC: 11352355. DOI: 10.3390/cimb46080508.

Natural Product-Derived Compounds Targeting Keratinocytes and Molecular Pathways in Psoriasis Therapeutics.

Lee Y, Jung Y, Choi H, Lee J, Lim T, Lee J Int J Mol Sci. 2024; 25(11).

PMID: 38892253 PMC: 11172960. DOI: 10.3390/ijms25116068.

Keratin 17 modulates the immune topography of pancreatic cancer.

Delgado-Coka L, Horowitz M, Torrente-Goncalves M, Roa-Pena L, Leiton C, Hasan M J Transl Med. 2024; 22(1):443.

PMID: 38730319 PMC: 11087249. DOI: 10.1186/s12967-024-05252-1.

Interplay of cytokines in the pathophysiology of atopic dermatitis: insights from Murin models and human.

Yamamura Y, Nakashima C, Otsuka A Front Med (Lausanne). 2024; 11:1342176.

PMID: 38590314 PMC: 10999685. DOI: 10.3389/fmed.2024.1342176.

References

Shen Z, Wang G, Fan J, Li W, Liu Y . HLA DR B1*04, *07-restricted epitopes on Keratin 17 for autoreactive T cells in psoriasis. J Dermatol Sci. 2005; 38(1):25-39. DOI: 10.1016/j.jdermsci.2005.01.001. View

Lowes M, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba L, Haider A . Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008; 128(5):1207-11. DOI: 10.1038/sj.jid.5701213. View

Jiang C, Flanagan S, Ohtsuki M, Shuai K, FREEDBERG I, Blumenberg M . Disease-activated transcription factor: allergic reactions in human skin cause nuclear translocation of STAT-91 and induce synthesis of keratin K17. Mol Cell Biol. 1994; 14(7):4759-69. PMC: 358849. DOI: 10.1128/mcb.14.7.4759-4769.1994. View

McFadden J, Baker B, Powles A, Fry L . Psoriasis and streptococci: the natural selection of psoriasis revisited. Br J Dermatol. 2009; 160(5):929-37. DOI: 10.1111/j.1365-2133.2009.09102.x. View

Wolk K, Haugen H, Xu W, Witte E, Waggie K, Anderson M . IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med (Berl). 2009; 87(5):523-36. DOI: 10.1007/s00109-009-0457-0. View

Wolk K, Kunz S, Witte E, Friedrich M, Asadullah K, Sabat R . IL-22 increases the innate immunity of tissues. Immunity. 2004; 21(2):241-54. DOI: 10.1016/j.immuni.2004.07.007. View

Liang S, Tan X, Luxenberg D, Karim R, Dunussi-Joannopoulos K, Collins M . Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006; 203(10):2271-9. PMC: 2118116. DOI: 10.1084/jem.20061308. View

Laatikainen L, Incoronato M, Castellone M, Laurila J, Santoro M, Laukkanen M . SOD3 decreases ischemic injury derived apoptosis through phosphorylation of Erk1/2, Akt, and FoxO3a. PLoS One. 2011; 6(8):e24456. PMC: 3164207. DOI: 10.1371/journal.pone.0024456. View

Xie M, Aggarwal S, Ho W, Foster J, Zhang Z, Stinson J . Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. J Biol Chem. 2000; 275(40):31335-9. DOI: 10.1074/jbc.M005304200. View

10.

Werner S, Smola H . Paracrine regulation of keratinocyte proliferation and differentiation. Trends Cell Biol. 2001; 11(4):143-6. DOI: 10.1016/s0962-8924(01)01955-9. View

11.

Boniface K, Bernard F, Garcia M, Gurney A, Lecron J, Morel F . IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol. 2005; 174(6):3695-702. DOI: 10.4049/jimmunol.174.6.3695. View

12.

Eyerich S, Eyerich K, Pennino D, Carbone T, Nasorri F, Pallotta S . Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest. 2009; 119(12):3573-85. PMC: 2786807. DOI: 10.1172/JCI40202. View

13.

Ma H, Liang S, Li J, Napierata L, Brown T, Benoit S . IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest. 2008; 118(2):597-607. PMC: 2200300. DOI: 10.1172/JCI33263. View

14.

Shi X, Jin L, Dang E, Chang T, Feng Z, Liu Y . IL-17A upregulates keratin 17 expression in keratinocytes through STAT1- and STAT3-dependent mechanisms. J Invest Dermatol. 2011; 131(12):2401-8. DOI: 10.1038/jid.2011.222. View

15.

Oshea J, Notarangelo L, Johnston J, Candotti F . Advances in the understanding of cytokine signal transduction: the role of Jaks and STATs in immunoregulation and the pathogenesis of immunodeficiency. J Clin Immunol. 1998; 17(6):431-47. DOI: 10.1023/a:1027388508570. View

16.

Mak R, Hundhausen C, Nestle F . Progress in understanding the immunopathogenesis of psoriasis. Actas Dermosifiliogr. 2010; 100 Suppl 2:2-13. PMC: 2957885. DOI: 10.1016/s0001-7310(09)73372-1. View

17.

Wilson N, Boniface K, Chan J, McKenzie B, Blumenschein W, Mattson J . Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol. 2007; 8(9):950-7. DOI: 10.1038/ni1497. View

18.

Haase I, Hobbs R, Romero M, Broad S, Watt F . A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis. J Clin Invest. 2001; 108(4):527-36. PMC: 209397. DOI: 10.1172/JCI12153. View

19.

Bockelmann R, Horn T, Gollnick H, Bonnekoh B . Interferon-gamma-dependent in vitro model for the putative keratin 17 autoimmune loop in psoriasis: exploration of pharmaco- and gene-therapeutic effects. Skin Pharmacol Physiol. 2004; 18(1):42-54. DOI: 10.1159/000081685. View

20.

Di Cesare A, Di Meglio P, Nestle F . The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009; 129(6):1339-50. DOI: 10.1038/jid.2009.59. View