Abstract
Psoriasis is a chronic, relapsing, immune-mediated, and papulosquamous skin disorder. Excessive mast cell activation, in psoriatic lesions, contributes to inflammation. Various endogenous peptides can participate in the pathogenesis of inflammatory diseases by activating mast cells. Suprabasin (SBSN) is expressed in multiple epithelial tissues and it regulates the normal epidermal barrier function. We have recently shown that suprabasin-derived polypeptides, SBSN(50-63), are significantly increased in psoriatic lesions, through differential peptide analysis. This study was conducted to clarify whether SBSN(50-63) plays a pivotal role in activating mast cells and mediating proinflammatory cytokines and chemokines production in psoriasis. The increased expression of SBSN in psoriatic lesions was confirmed by bioinformatics analysis, PCR and ELISA. Wild-type mice injected subcutaneously with SBSN(50-63) exhibited infiltration of inflammatory cells and the release of cytokines in vivo. SBSN(50-63) stimulated mouse primary mast cells (MPMC) and the laboratory of allergic disease 2 (LAD2) human mast cells to produce more inflammatory mediators than the control group, which were measured ex vivo and in vitro. Toll-like receptor 4 was identified as the receptor of SBSN on mast cells by molecular docking analysis, molecular dynamics simulation, and siRNA transfection. Collectively, SBSN(50-63) could activate mast cells through TLR4, which may increase the inflammatory response in psoriasis.
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References
Alam MT, Nagao-Kitamoto H, Ohga N et al (2019) Suprabasin as a novel tumor endothelial cell marker. Cancer Sci 105:1533–1540
Aoshima M, Phadungsaksawasdi P, Nakazawa S et al (2019) Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis. J Dermatol Sci 95:107–112. https://doi.org/10.1016/j.jdermsci.2019.07.009
Aung G, Niyonsaba F, Ushio H et al (2011) Catestatin, a neuroendocrine antimicrobial peptide, induces human mast cell migration, degranulation and production of cytokines and chemokines: catestatin activates human mast cells. Immunology 132:527–539. https://doi.org/10.1111/j.1365-2567.2010.03395.x
Boehncke WH, Schön MP (2015) Psoriasis. Lancet 386:983–994. https://doi.org/10.1016/S0140-6736(14)61909-7
Conti P, Pregliasco FE, Bellomo RG et al (2021) Mast cell cytokines IL-1, IL-33, and IL-36 mediate skin inflammation in psoriasis: a novel therapeutic approach with the anti-inflammatory cytokines IL-37, IL-38, and IL-1Ra. IJMS 22:8076. https://doi.org/10.3390/ijms22158076
da CarvalhoNilsson RFGS, Harvima IT (2010) Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation. Exp Dermatol 19:117–122. https://doi.org/10.1111/j.1600-0625.2009.00998.x
Dudeck J, Kotrba J, Immler R et al (2021) Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation. Immunity 54:468-483.e5. https://doi.org/10.1016/j.immuni.2020.12.017
Duraisamy K, Singh K, Kumar M et al (2022) P17 induces chemotaxis and differentiation of monocytes via MRGPRX2-mediated mast cell-line activation. J Allergy Clin Immunol 149:275–291. https://doi.org/10.1016/j.jaci.2021.04.040
Flutter B, Nestle FO (2013) TLRs to cytokines: mechanistic insights from the imiquimod mouse model of psoriasis: HIGHLIGHTS. Eur J Immunol 43:3138–3146. https://doi.org/10.1002/eji.201343801
Garzorz-Stark N, Eyerich K (2019) psoriasis pathogenesis: keratinocytes are back in the spotlight. J Investig Dermatol 139:995–996. https://doi.org/10.1016/j.jid.2019.01.026
Green DP, Limjunyawong N, Gour N et al (2019) A mast-cell-specific receptor mediates neurogenic inflammation and pain. Neuron 101:412-420.e3. https://doi.org/10.1016/j.neuron.2019.01.012
Griffiths CEM, Armstrong AW, Gudjonsson JE et al (2021) Psoriasis. Lancet 397:1301–1315. https://doi.org/10.1016/S0140-6736(20)32549-6
Hao Y, Peng B, Che D et al (2020) Imiquimod-related dermatitis is mainly mediated by mast cell degranulation via Mas-related G-protein coupled receptor B2. Int Immunopharmacol 81:106258. https://doi.org/10.1016/j.intimp.2020.106258
Heib V, Becker M, Warger T et al (2007) Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice. Blood 110:946–953. https://doi.org/10.1182/blood-2006-07-036889
Herster F, Bittner Z, Archer NK et al (2020) Neutrophil extracellular trap-associated RNA and LL37 enable self-amplifying inflammation in psoriasis. Nat Commun 11:105. https://doi.org/10.1038/s41467-019-13756-4
Hwang T-L (2019) Neutrophils in psoriasis. Front Immunol 10:12
Karhu T, Akiyama K, Vuolteenaho O et al (2017) Mast cell degranulation via MRGPRX2 by isolated human albumin fragments. Biochimica Et Biophysica Acta (BBA) General Subjects 1861:2530–2534. https://doi.org/10.1016/j.bbagen.2017.08.013
Lin AM, Rubin CJ, Khandpur R et al (2011) Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol 187:490–500. https://doi.org/10.4049/jimmunol.1100123
Lowes MA, Russell CB, Martin DA et al (2013) The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol 34:174–181. https://doi.org/10.1016/j.it.2012.11.005
Mashiko S, Bouguermouh S, Rubio M et al (2015) Human mast cells are major IL-22 producers in patients with psoriasis and atopic dermatitis. J Allergy Clin Immunol 136:351-359.e1. https://doi.org/10.1016/j.jaci.2015.01.033
Matsui T, Hayashi-Kisumi F, Kinoshita Y et al (2004) Identification of novel keratinocyte-secreted peptides dermokine-alpha/-beta and a new stratified epithelium-secreted protein gene complex on human chromosome 19q13.1. Genomics 84:384–397
Nakazawa S, Shimauchi T, Funakoshi A et al (2020) Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading. Sci Rep 10:14559. https://doi.org/10.1038/s41598-020-71536-3
Pribyl M, Hodny Z, Kubikova I (2021) Suprabasin—a Review. Genes 12:108. https://doi.org/10.3390/genes12010108
Rendon A, Schäkel K (2019) Psoriasis pathogenesis and treatment. Int J Mol Sci 20:1475. https://doi.org/10.3390/ijms20061475
Sandig H, Bulfone-Paus S (2012) TLR signaling in mast cells: common and unique features. Front Immun 3:185. https://doi.org/10.3389/fimmu.2012.00185
Sciani JM, Sampaio MC, Zychar BC et al (2014) Echinometrin: a novel mast cell degranulating peptide from the coelomic liquid of echinometra lucunter sea urchin. Peptides 53:13–21. https://doi.org/10.1016/j.peptides.2013.07.031
Siiskonen H, Harvima I (2019) Mast cells and sensory nerves contribute to neurogenic inflammation and pruritus in chronic skin inflammation. Front Cell Neurosci 13:422. https://doi.org/10.3389/fncel.2019.00422
Subramanian H, Gupta K, Lee D et al (2013) β-Defensins activate human mast cells via mas-related gene X2. J Immunol 191:345–352. https://doi.org/10.4049/jimmunol.1300023
Tan H, Wang L, Liu Z (2022) Suprabasin: role in human cancers and other diseases. Mol Biol Rep 49:1453–1461
Wang A, Bai Y (2020) Dendritic cells: the driver of psoriasis. J Dermatol 47:104–113. https://doi.org/10.1111/1346-8138.15184
Yu Y, Zhang Y, Zhang Y et al (2017) LL-37-induced human mast cell activation through G protein-coupled receptor MrgX2. Int Immunopharmacol 49:6–12. https://doi.org/10.1016/j.intimp.2017.05.016
Zhou T, Du X, Zhang L et al (2022) Suprabasin derived polypeptides: SBSN(50–63) induced inflammatory reaction by activation mast cells via TLR4. J Investig Dermatol 142(8):B2
Zhu J, Wu G, Li Q et al (2016) Overexpression of suprabasin is associated with proliferation and tumorigenicity of esophageal squamous cell carcinoma. Sci Rep 6:21549. https://doi.org/10.1038/srep21549
Funding
This work was supported by the National Natural Science Foundation of China (Grant Number: 82073451). Innovation Capability Support Program of Shaanxi (Program No.2022TD-48). Natural Science Basic Research Program of Shaanxi (Program No. 2022JQ-956). Key R&D plan of Shaanxi Province (Grant Number: 2020SF-175).
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All authors contributed to the study conception and design. Material preparation and data collection were performed by Tong Zhou, Xueshan Du, Xiangjin Song and Delu Che. Software and formal analysis were performed by Lei Zhang, Yi Zheng and Tao Jia. The first draft of the manuscript was written by Tong Zhou. Reviewed and edited by Songmei Geng, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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In accordance with Xi’an Jiaotong University (Xi’an, Shaanxi, China) research guidelines and policies, we obtained the informed consent of the patient's parents.
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All of the animal procedures were conducted according to the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and approved by Animal Ethics Committee (Permit Number: XJTU 2021-1025) of Xi’an Jiaotong University. The Chinese Clinical Trial Registry received the registration of this study (Registration Number: ChiCTR2100052365). All experimental procedures using human samples were approved by Xi’an Jiaotong University Ethics Committee.
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Zhou, T., Du, X., Zhang, L. et al. Suprabasin-derived polypeptides: SBSN(50-63) induces inflammatory response via TLR4-mediated mast cell activation. Inflammopharmacol 31, 1329–1339 (2023). https://doi.org/10.1007/s10787-023-01137-9
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DOI: https://doi.org/10.1007/s10787-023-01137-9