Among the ~22,000 human genes, very few remain that have unknown functions. One such example is suprabasin (SBSN). Originally described as a component of the cornified envelope, the function of stratified epithelia-expressed SBSN is unknown. Both the lack of knowledge about the gene role under physiological conditions and the emerging link of SBSN to various human diseases, including cancer, attract research interest. The association of SBSN expression with poor prognosis of patients suffering from oesophageal carcinoma, glioblastoma multiforme, and myelodysplastic syndromes suggests that SBSN may play a role in human tumourigenesis. Three SBSN isoforms code for the secreted proteins with putative function as signalling molecules, yet with poorly described effects. In this first review about SBSN, we summarised the current knowledge accumulated since its original description, and we discuss the potential mechanisms and roles of SBSN in both physiology and pathology.

Laboratory of Genome Integrity Institute of Molecular Genetics of the Czech Academy of Sciences Videnska 1083 14220 Prague Czech Republic

Zobrazit více v PubMed

Park G.T., Lim S.E., Jang S.I., Morasso M.I. Suprabasin, a novel epidermal differentiation marker and potential cornified envelope precursor. J. Biol. Chem. 2002;277:45195–45202. doi: 10.1074/jbc.M205380200. PubMed DOI PMC

Matsui T., Hayashi-Kisumi F., Kinoshita Y., Katahira S., Morita K., Miyachi Y., Ono Y., Imai T., Tanigawa Y., Komiya T., et al. Identification of novel keratinocyte-secreted peptides dermokine-α/- β and a new stratified epithelium-secreted protein gene complex on human chromosome 19q13.1. Genomics. 2004;84:384–397. doi: 10.1016/j.ygeno.2004.03.010. PubMed DOI

Hunt S.E., McLaren W., Gil L., Thormann A., Schuilenburg H., Sheppard D., Parton A., Armean I.M., Trevanion S.J., Flicek P., et al. Ensembl variation resources. Database. 2018;2018 doi: 10.1093/database/bay119. PubMed DOI PMC

Kumar S., Stecher G., Li M., Knyaz C., Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol. Biol. Evol. 2018;35:1547–1549. doi: 10.1093/molbev/msy096. PubMed DOI PMC

Clark H.F. The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment. Genome Res. 2003;13:2265–2270. doi: 10.1101/gr.1293003. PubMed DOI PMC

Consortium T.U. Activities at the Universal Protein Resource (UniProt) Nucleic Acids Res. 2014;42:D191–D198. doi: 10.1093/nar/gkt1140. PubMed DOI PMC

Moffatt P., Salois P., St-Amant N., Gaumond M.H., Lanctôt C. Identification of a conserved cluster of skin-specific genes encoding secreted proteins. Gene. 2004;334:123–131. doi: 10.1016/j.gene.2004.03.010. PubMed DOI

Sancandi M., Uysal-Onganer P., Kraev I., Mercer A., Lange S. Protein deimination signatures in plasma and plasma-evs and protein deimination in the brain vasculature in a rat model of pre-motor parkinson’s disease. Int. J. Mol. Sci. 2020;21:2743. doi: 10.3390/ijms21082743. PubMed DOI PMC

Steentoft C., Vakhrushev S.Y., Joshi H.J., Kong Y., Vester-Christensen M.B., Schjoldager K.T.-B.G., Lavrsen K., Dabelsteen S., Pedersen N.B., Marcos-Silva L., et al. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology. EMBO J. 2013;32:1478–1488. doi: 10.1038/emboj.2013.79. PubMed DOI PMC

Kelley L.A., Mezulis S., Yates C.M., Wass M.N., Michael J.E.S. The Phyre2 web portal for protein modeling, prediction and analysis. Nat. Protoc. 2016;10:845–858. doi: 10.1038/nprot.2015.053. PubMed DOI PMC

Mathelier A., Zhao X., Zhang A.W., Parcy F., Worsley-Hunt R., Arenillas D.J., Buchman S., Chen C.Y., Chou A., Ienasescu H., et al. JASPAR 2014: An extensively expanded and updated open-access database of transcription factor binding profiles. Nucleic Acids Res. 2014;42:142–147. doi: 10.1093/nar/gkt997. PubMed DOI PMC

Takahashi K., Asano N., Imatani A., Kondo Y., Saito M., Takeuchi A., Jin X., Saito M., Hatta W., Asanuma K., et al. Sox2 induces tumorigenesis and angiogenesis of early stage esophagealsquamous cell carcinoma through secretion of Suprabasin. Carcinogenesis. 2020;26:1–15. doi: 10.1093/carcin/bgaa014. PubMed DOI

Gaykalova D., Vatapalli R., Glazer C.A., Bhan S., Shao C., Sidransky D., Ha P.K., Califano J.A. Dose-Dependent Activation of Putative Oncogene SBSN by BORIS. PLoS ONE. 2012;7:e40389. doi: 10.1371/journal.pone.0040389. PubMed DOI PMC

Li J., Zheng L., Uchiyama A., Bin L., Mauro T.M., Elias P.M., Pawelczyk T., Sakowicz-Burkiewicz M., Trzeciak M., Leung D.Y.M., et al. A data mining paradigm for identifying key factors in biological processes using gene expression data. Sci. Rep. 2018;8:9083. doi: 10.1038/s41598-018-27258-8. PubMed DOI PMC

Uhlen M., Fagerberg L., Hallstrom B.M., Lindskog C., Oksvold P., Mardinoglu A., Sivertsson A., Kampf C., Sjostedt E., Asplund A., et al. Tissue-based map of the human proteome. Science. 2015;347:1260419. doi: 10.1126/science.1260419. PubMed DOI

Bazzi H., Fantauzzo K.A., Richardson G.D., Jahoda C.A.B., Christiano A.M. Transcriptional profiling of developing mouse epidermis reveals novel patterns of coordinated gene expression. Dev. Dyn. 2007;236:961–970. doi: 10.1002/dvdy.21099. PubMed DOI

Brass E.P., Peters M.A., Hinchcliff K.W., He Y.D., Ulrich R.G. Temporal pattern of skeletal muscle gene expression following endurance exercise in Alaskan sled dogs. J. Appl. Physiol. 2009;107:605–612. doi: 10.1152/japplphysiol.91347.2008. PubMed DOI

Ichinose K., Ohyama K., Furukawa K., Higuchi O., Mukaino A., Satoh K., Nakane S., Shimizu T., Umeda M., Fukui S., et al. Novel anti-suprabasin antibodies may contribute to the pathogenesis of neuropsychiatric systemic lupus erythematosus. Clin. Immunol. 2018;193:123–130. doi: 10.1016/j.clim.2017.11.006. PubMed DOI

Hubackova S., Pribyl M., Kyjacova L., Moudra A., Dzijak R., Salovska B., Strnad H., Tambor V., Imrichova T., Svec J., et al. Interferon-regulated suprabasin is essential for stress-induced stem-like cell conversion and therapy resistance of human malignancies. Mol. Oncol. 2019;13:1467–1489. doi: 10.1002/1878-0261.12480. PubMed DOI PMC

Mehic D., Bakiri L., Ghannadan M., Wagner E.F., Tschachler E. Fos and Jun Proteins Are Specifically Expressed During Differentiation of Human Keratinocytes. J. Investig. Dermatol. 2005;124:212–220. doi: 10.1111/j.0022-202X.2004.23558.x. PubMed DOI

Connelly J.T., Gautrot J.E., Trappmann B., Tan D.W.-M., Donati G., Huck W.T.S., Watt F.M. Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions. Nat. Cell Biol. 2010;12:711–718. doi: 10.1038/ncb2074. PubMed DOI

Zhu A.J., Watt F.M. beta-catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development. 1999;126:2285–2298. PubMed

Dubash A.D., Koetsier J.L., Amargo E.V., Najor N.A., Harmon R.M., Green K.J. The GEF Bcr activates RhoA/MAL signaling to promote keratinocyte differentiation via desmoglein-1. J. Cell Biol. 2013;202:653–666. doi: 10.1083/jcb.201304133. PubMed DOI PMC

Luxenburg C., Pasolli H.A., Williams S.E., Fuchs E. Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation. Nat. Cell Biol. 2011;13:203–214. doi: 10.1038/ncb2163. PubMed DOI PMC

Alam M.T., Nagao-Kitamoto H., Ohga N., Akiyama K., Maishi N., Kawamoto T., Shinohara N., Taketomi A., Shindoh M., Hida Y., et al. Suprabasin as a novel tumor endothelial cell marker. Cancer Sci. 2014;105:1533–1540. doi: 10.1111/cas.12549. PubMed DOI PMC

Nguyen L.N., Novak N., Baumann M., Koehn J., Borth N. Bioinformatic Identification of Chinese Hamster Ovary (CHO) Cold-Shock Genes and Biological Evidence of their Cold-Inducible Promoters. Biotechnol. J. 2019:e1900359. doi: 10.1002/biot.201900359. PubMed DOI

Thaisuchat H., Baumann M., Pontiller J., Hesse F., Ernst W. Identification of a novel temperature sensitive promoter in cho cells. BMC Biotechnol. 2011;11:51. doi: 10.1186/1472-6750-11-51. PubMed DOI PMC

Goyal R., Longo L.D. Acclimatization to long-term hypoxia: Gene expression in ovine carotid arteries. Physiol. Genom. 2014;46:725–734. doi: 10.1152/physiolgenomics.00073.2014. PubMed DOI PMC

Zhu J., Wu G., Li Q., Gong H., Song J., Cao L., Wu S., Song L., Jiang L. Overexpression of Suprabasin is Associated with Proliferation and Tumorigenicity of Esophageal Squamous Cell Carcinoma. Sci. Rep. 2016;6:21549. doi: 10.1038/srep21549. PubMed DOI PMC

Ghosh S., Dean A., Walter M., Bao Y., Hu Y., Ruan J., Li R. Cell density-dependent transcriptional activation of endocrine-related genes in human adipose tissue-derived stem cells. Exp. Cell Res. 2010;316:2087–2098. doi: 10.1016/j.yexcr.2010.04.015. PubMed DOI PMC

Stanton A., Mowbray C., Lanz M., Brown K., Hilton P., Tyson-Capper A., Pickard R.S., Ali A.S.M., Hall J. Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin. Sci. Rep. 2020;10:8473. doi: 10.1038/s41598-020-64291-y. PubMed DOI PMC

Pribyl M., Hubackova S., Moudra A., Vancurova M., Polackova H., Stopka T., Jonasova A., Bokorova R., Fuchs O., Stritesky J., et al. Aberrantly elevated suprabasin in the bone marrow as a candidate biomarker of advanced disease state in myelodysplastic syndromes. Mol. Oncol. 2020;14:2403–2419. doi: 10.1002/1878-0261.12768. PubMed DOI PMC

Glazer C.A., Smith I.M., Ochs M.F., Begum S., Westra W., Chang S.S., Sun W., Bhan S., Khan Z., Ahrendt S., et al. Integrative Discovery of Epigenetically Derepressed Cancer Testis Antigens in NSCLC. PLoS ONE. 2009;4:e8189. doi: 10.1371/journal.pone.0008189. PubMed DOI PMC

Shao C., Tan M., Bishop J.A., Liu J., Bai W., Gaykalova D.A., Ogawa T., Vikani A.R., Agrawal Y., Li R.J., et al. Suprabasin Is Hypomethylated and Associated with Metastasis in Salivary Adenoid Cystic Carcinoma. PLoS ONE. 2012;7:1–7. doi: 10.1371/journal.pone.0048582. PubMed DOI PMC

Sangwung P., Zhou G., Nayak L., Chan E.R., Kumar S., Kang D.-W., Zhang R., Liao X., Lu Y., Sugi K., et al. KLF2 and KLF4 control endothelial identity and vascular integrity. JCI Insight. 2017;2:e91700. doi: 10.1172/jci.insight.91700. PubMed DOI PMC

Nakazawa S., Shimauchi T., Funakoshi A., Aoshima M., Phadungsaksawasdi P., Sakabe J., Asakawa S., Hirasawa N., Ito T., Tokura Y. Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading. Sci. Rep. 2020;10:14559. doi: 10.1038/s41598-020-71536-3. PubMed DOI PMC

Aoshima M., Phadungsaksawasdi P., Nakazawa S., Iwasaki M., Sakabe J., Umayahara T., Yatagai T., Ikeya S., Shimauchi T., Tokura Y. Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis. J. Dermatol. Sci. 2019;95:107–112. doi: 10.1016/j.jdermsci.2019.07.009. PubMed DOI

Formolo C.A., Williams R., Gordish-Dressman H., MacDonald T.J., Lee N.H., Hathout Y. Secretome signature of invasive glioblastoma multiforme. J. Proteome Res. 2011;10:3149–3159. doi: 10.1021/pr200210w. PubMed DOI PMC

Sheng S.H., Zhu H.L. Proteomic analysis of pleural effusion from lung adenocarcinoma patients by shotgun strategy. Clin. Transl. Oncol. 2014;16:153–157. doi: 10.1007/s12094-013-1054-9. PubMed DOI

Ambekar A.S., Kelkar D.S., Pinto S.M., Sharma R., Hinduja I., Zaveri K., Pandey A., Prasad T.S.K., Gowda H., Mukherjee S. Proteomics of follicular fluid from women with polycystic ovary syndrome suggests molecular defects in follicular development. J. Clin. Endocrinol. Metab. 2015;100:744–753. doi: 10.1210/jc.2014-2086. PubMed DOI PMC

Kuuselo R., Simon R., Karhu R., Tennstedt P., Marx A.H., Izbicki J.R., Yekebas E., Sauter G., Kallioniemi A. 19q13 amplification is associated with high grade and stage in pancreatic cancer. Genes. Chromosom. Cancer. 2010;49:569–575. doi: 10.1002/gcc.20767. PubMed DOI PMC

Thompson F.H., Nelson M.A., Trent J.M., Guan X.-Y., Liu Y., Yang J.-M., Emerson J., Adair L., Wymer J., Balfour C., et al. Amplification of 19q13.1–q13.2 sequences in ovarian cancer. Cancer Genet. Cytogenet. 1996;87:55–62. doi: 10.1016/0165-4608(95)00248-0. PubMed DOI

Muleris M., Almeida A., Gerbault-Seureau M., Malfoy B., Dutrillaux B. Identification of amplified DNA sequences in breast cancer and their organization within homogeneously staining regions. Genes Chromosom. Cancer. 1995;14:155–163. doi: 10.1002/gcc.2870140302. PubMed DOI

Rao P.H., Arias-Pulido H., Lu X.-Y., Harris C.P., Vargas H., Zhang F.F., Narayan G., Schneider A., Terry M.B., Murty V.V. Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma. BMC Cancer. 2004;4:5. doi: 10.1186/1471-2407-4-5. PubMed DOI PMC

Hong J.A., Kang Y., Abdullaev Z., Flanagan P.T., Pack S.D., Fischette M.R., Adnani M.T., Loukinov D.I., Vatolin S., Risinger J.I., et al. Reciprocal Binding of CTCF and BORIS to the NY-ESO-1 Promoter Coincides with Derepression of this Cancer-Testis Gene in Lung Cancer Cells. Cancer Res. 2005;65:7763–7774. doi: 10.1158/0008-5472.CAN-05-0823. PubMed DOI

Vatolin S., Abdullaev Z., Pack S.D., Flanagan P.T., Custer M., Loukinov D.I., Pugacheva E., Hong J.A., Morse H., Schrump D.S., et al. Conditional Expression of the CTCF-Paralogous Transcriptional Factor BORIS in Normal Cells Results in Demethylation and Derepression of MAGE-A1 and Reactivation of Other Cancer-Testis Genes. Cancer Res. 2005;65:7751–7762. doi: 10.1158/0008-5472.CAN-05-0858. PubMed DOI

Bhan S., Negi S.S., Shao C., Glazer C.A., Chuang A., Gaykalova D.A., Sun W., Sidransky D., Ha P.K., Califano J.A. BORIS Binding to the Promoters of Cancer Testis Antigens, MAGEA2, MAGEA3, and MAGEA4, Is Associated with Their Transcriptional Activation in Lung Cancer. Clin. Cancer Res. 2011;17:4267–4276. doi: 10.1158/1078-0432.CCR-11-0653. PubMed DOI PMC

Soltanian S., Dehghani H. BORIS: A key regulator of cancer stemness. Cancer Cell Int. 2018;18:154. doi: 10.1186/s12935-018-0650-8. PubMed DOI PMC

Jiang S., Zhang Q., Su Y., Pan L. Network-Based Differential Analysis to Identify Molecular Features of Tumorigenesis for Esophageal Squamous Carcinoma. Molecules. 2018;23:88. doi: 10.3390/molecules23010088. PubMed DOI PMC

Kenagy R.D., Civelek M., Kikuchi S., Chen L., Grieff A., Sobel M., Lusis A.J., Clowes A.W. Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency. J. Vasc. Surg. 2016;64:202–209.e6. doi: 10.1016/j.jvs.2014.12.052. PubMed DOI PMC

Bowman R.L., Wang Q., Carro A., Verhaak R.G.W., Squatrito M. GlioVis data portal for visualization and analysis of brain tumor expression datasets. Neuro Oncol. 2017;19:139–141. doi: 10.1093/neuonc/now247. PubMed DOI PMC

Behnan J., Finocchiaro G., Hanna G. The landscape of the mesenchymal signature in brain tumours. Brain. 2019;142:847–866. doi: 10.1093/brain/awz044. PubMed DOI PMC

Liu B., Huang G., Zhu H., Ma Z., Tian X., Yin L., Gao X., He X. Analysis of gene co-expression network reveals prognostic significance of CNFN in patients with head and neck cancer. Oncol. Rep. 2019;41:2168–2180. doi: 10.3892/or.2019.7019. PubMed DOI PMC

Winter S., Shoaie S., Kordasti S., Platzbecker U. Integrating the “Immunome” in the Stratification of Myelodysplastic Syndromes and Future Clinical Trial Design. J. Clin. Oncol. 2020;38:1723–1735. doi: 10.1200/JCO.19.01823. PubMed DOI

Chrastinová L., Pastva O., Bocková M., Lynn N.S., Šácha P., Hubálek M., Suttnar J., Kotlín R., Štikarová J., Hlaváčková A., et al. A New Approach for the Diagnosis of Myelodysplastic Syndrome Subtypes Based on Protein Interaction Analysis. Sci. Rep. 2019;9:12647. doi: 10.1038/s41598-019-49084-2. PubMed DOI PMC

Druhan L.J., Lance A., Li S., Price A.E., Emerson J.T., Baxter S.A., Gerber J.M., Avalos B.R. Leucine Rich α-2 Glycoprotein: A Novel Neutrophil Granule Protein and Modulator of Myelopoiesis. PLoS ONE. 2017;12:e0170261. doi: 10.1371/journal.pone.0170261. PubMed DOI PMC

Wang X., Abraham S., McKenzie J.A.G., Jeffs N., Swire M., Tripathi V.B., Luhmann U.F.O., Lange C.A.K., Zhai Z., Arthur H.M., et al. LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling. Nature. 2013;499:306–311. doi: 10.1038/nature12345. PubMed DOI PMC

Campos D., Freitas D., Gomes J., Magalhães A., Steentoft C., Gomes C., Vester-Christensen M.B., Ferreira J.A., Afonso L.P., Santos L.L., et al. Probing the O-Glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery. Mol. Cell. Proteom. 2015;14:1616–1629. doi: 10.1074/mcp.M114.046862. PubMed DOI PMC

Chen X., Eksioglu E.A., Zhou J., Zhang L., Djeu J., Fortenbery N., Epling-Burnette P., Van Bijnen S., Dolstra H., Cannon J., et al. Induction of myelodysplasia by myeloid-derived suppressor cells. J. Clin. Investig. 2013;123:4595–4611. doi: 10.1172/JCI67580. PubMed DOI PMC

Sallman D.A., List A. The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes. Blood. 2019;133:1039–1048. doi: 10.1182/blood-2018-10-844654. PubMed DOI PMC

Ku T.K.S., Crowe D.L. Impaired T lymphocyte function increases tumorigenicity and decreases tumor latency in a mouse model of head and neck cancer. Int. J. Oncol. 2009;35:1211–1221. doi: 10.3892/ijo_00000438. PubMed DOI

Fugmann T., Sofron A., Ritz D., Bootz F., Neri D. The MHC Class II Immunopeptidome of Lymph Nodes in Health and in Chemically Induced Colitis. J. Immunol. 2017;198:1357–1364. doi: 10.4049/jimmunol.1601157. PubMed DOI PMC

Richardson M.R., Segu Z.M., Price M.O., Lai X., Witzmann F.A., Mechref Y., Yoder M.C., Price F.W. Alterations in the aqueous humor proteome in patients with Fuchs endothelial corneal dystrophy. Mol. Vis. 2010;16:2376–2383. PubMed PMC

Nanda G.G., Alone D.P. REVIEW: Current understanding of the pathogenesis of Fuchs’ endothelial corneal dystrophy. Mol. Vis. 2019;25:295–310. PubMed PMC

Liu L., Watanabe N., Akatsu H., Nishimura M. Neuronal expression of ILEI/FAM3C and its reduction in Alzheimer’s disease. Neuroscience. 2016;330:236–246. doi: 10.1016/j.neuroscience.2016.05.050. PubMed DOI

Theriot C.A., Zanello S.B. Molecular Effects of Spaceflight in the Mouse Eye after Space Shuttle Mission. Gravit. Space Res. 2014;2:3–24.

Mao X., Byrum S., Nishiyama N., Pecaut M., Sridharan V., Boerma M., Tackett A., Shiba D., Shirakawa M., Takahashi S., et al. Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis. Int. J. Mol. Sci. 2018;19:2546. doi: 10.3390/ijms19092546. PubMed DOI PMC

Mao X.W., Nishiyama N.C., Byrum S.D., Stanbouly S., Jones T., Drew A., Sridharan V., Boerma M., Tackett A.J., Zawieja D., et al. Characterization of mouse ocular response to a 35-day spaceflight mission: Evidence of blood-retinal barrier disruption and ocular adaptations. Sci. Rep. 2019;9:8215. doi: 10.1038/s41598-019-44696-0. PubMed DOI PMC

Chidambaram J.D., Kannambath S., Srikanthi P., Shah M., Lalitha P., Elakkiya S., Bauer J., Prajna N.V., Holland M.J., Burton M.J. Persistence of Innate Immune Pathways in Late Stage Human Bacterial and Fungal Keratitis: Results from a Comparative Transcriptome Analysis. Front. Cell. Infect. Microbiol. 2017;7:193. doi: 10.3389/fcimb.2017.00193. PubMed DOI PMC

Diamanti-Kandarakis E., Alexandraki K., Piperi C., Protogerou A., Katsikis I., Paterakis T., Lekakis J., Panidis D. Inflammatory and endothelial markers in women with polycystic ovary syndrome. Eur. J. Clin. Investig. 2006;36:691–697. doi: 10.1111/j.1365-2362.2006.01712.x. PubMed DOI

Orio F., Palomba S., Spinelli L., Cascella T., Tauchmanovà L., Zullo F., Lombardi G., Colao A. The Cardiovascular Risk of Young Women with Polycystic Ovary Syndrome: An Observational, Analytical, Prospective Case-Control Study. J. Clin. Endocrinol. Metab. 2004;89:3696–3701. doi: 10.1210/jc.2003-032049. PubMed DOI

Kelly C.C.J., Lyall H., Petrie J.R., Gould G.W., Connell J.M.C., Sattar N. Low Grade Chronic Inflammation in Women with Polycystic Ovarian Syndrome. J. Clin. Endocrinol. Metab. 2001;86:2453–2455. doi: 10.1210/jcem.86.6.7580. PubMed DOI

Ishigami A., Maruyama N. Importance of research on peptidylarginine deiminase and citrullinated proteins in age-related disease. Geriatr. Gerontol. Int. 2010;10:S53–S58. doi: 10.1111/j.1447-0594.2010.00593.x. PubMed DOI

Valesini G., Gerardi M.C., Iannuccelli C., Pacucci V.A., Pendolino M., Shoenfeld Y. Citrullination and autoimmunity. Autoimmun. Rev. 2015;14:490–497. doi: 10.1016/j.autrev.2015.01.013. PubMed DOI

Liu S., Zhou X., Peng X., Li M., Ren B., Cheng G., Cheng L. Porphyromonas gingivalis Promotes Immunoevasion of Oral Cancer by Protecting Cancer from Macrophage Attack. J. Immunol. 2020;205:282–289. doi: 10.4049/jimmunol.1901138. PubMed DOI

Mahendra J., Mahendra L., Kurian V.M., Jaishankar K., Mythilli R. Prevalence of periodontal pathogens in coronary atherosclerotic plaque of patients undergoing coronary artery bypass graft surgery. J. Maxillofac. Oral Surg. 2009;8:108–113. doi: 10.1007/s12663-009-0028-5. PubMed DOI PMC

Mougeot J.-L.C., Stevens C.B., Paster B.J., Brennan M.T., Lockhart P.B., Mougeot F.K.B. Porphyromonas gingivalis is the most abundant species detected in coronary and femoral arteries. J. Oral Microbiol. 2017;9:1281562. doi: 10.1080/20002297.2017.1281562. PubMed DOI PMC

Dominy S.S., Lynch C., Ermini F., Benedyk M., Marczyk A., Konradi A., Nguyen M., Haditsch U., Raha D., Griffin C., et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv. 2019;5:1–22. doi: 10.1126/sciadv.aau3333. PubMed DOI PMC

Haditsch U., Roth T., Rodriguez L., Hancock S., Cecere T., Nguyen M., Arastu-Kapur S., Broce S., Raha D., Lynch C.C., et al. Alzheimer’s Disease-Like Neurodegeneration in Porphyromonas gingivalis Infected Neurons with Persistent Expression of Active Gingipains. J. Alzheimer’s Dis. 2020;75:1361–1376. doi: 10.3233/JAD-200393. PubMed DOI PMC

Yoshio T., Okamoto H., Kurasawa K., Dei Y., Hirohata S., Minota S. IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus. Lupus. 2016;25:997–1003. doi: 10.1177/0961203316629556. PubMed DOI

Wang J.B., Li H., Wang L.L., Liang H.D., Zhao L., Dong J. Role of IL-1β, IL-6, IL-8 and IFN-γ in pathogenesis of central nervous system neuropsychiatric systemic lupus erythematous. Int. J. Clin. Exp. Med. 2015;8:16658–16663. PubMed PMC

Castillo C., Carrillo I., Libisch G., Juiz N., Schijman A., Robello C., Kemmerling U. Host-parasite interaction: Changes in human placental gene expression induced by Trypanosoma cruzi. Parasit. Vectors. 2018;11:479. doi: 10.1186/s13071-018-2988-0. PubMed DOI PMC

Lorey M.B., Rossi K., Eklund K.K., Nyman T.A., Matikainen S. Global characterization of protein secretion from human macrophages following non-canonical caspase-4/5 inflammasome activation. Mol. Cell. Proteom. 2017;16:S187–S199. doi: 10.1074/mcp.M116.064840. PubMed DOI PMC

Keegan C. Ph.D. Thesis. University of California; Oakland, CA, USA: 2016. Mycobacterium Tuberculosis tRNA Triggers TLR8 to Induce a Pathway for Th1 Cell Instruction.

Hummelen R., Macklaim J.M., Bisanz J.E., Hammond J.A., McMillan A., Vongsa R., Koenig D., Gloor G.B., Reid G. Vaginal microbiome and epithelial gene array in post-menopausal women with moderate to severe dryness. PLoS ONE. 2011;6:e26602. doi: 10.1371/journal.pone.0026602. PubMed DOI PMC

Orikasa S., Hinman F. Reaction of the vesical wall to bacterial penetration: Resistance to attachment, desquamation, and leukocytic activity. Investig. Urol. 1977;15:185–193. PubMed

Mulvey M.A. Induction and Evasion of Host Defenses by Type 1-Piliated Uropathogenic Escherichia coli. Science. 1998;282:1494–1497. doi: 10.1126/science.282.5393.1494. PubMed DOI

Reigstad C.S., Hultgren S.J., Gordon J.I. Functional genomic studies of uropathogenic Escherichia coli and host urothelial cells when intracellular bacterial communities are assembled. J. Biol. Chem. 2007;282:21259–21267. doi: 10.1074/jbc.M611502200. PubMed DOI

Carregaro F., Stefanini A.C.B., Henrique T., Tajara E.H. Study of small proline-rich proteins (SPRRs) in health and disease: A review of the literature. Arch. Dermatol. Res. 2013;305:857–866. doi: 10.1007/s00403-013-1415-9. PubMed DOI

Li R.W., Meyer M.J., Van Tassell C.P., Sonstegard T.S., Connor E.E., Van Amburgh M.E., Boisclair Y.R., Capuco A.V. Identification of estrogen-responsive genes in the parenchyma and fat pad of the bovine mammary gland by microarray analysis. Physiol. Genom. 2006;27:42–53. doi: 10.1152/physiolgenomics.00032.2006. PubMed DOI

Reilly S.M., Saltiel A.R. Adapting to obesity with adipose tissue inflammation. Nat. Rev. Endocrinol. 2017;13:633–643. doi: 10.1038/nrendo.2017.90. PubMed DOI

Brunner P.M., Guttman-Yassky E., Leung D.Y.M. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J. Allergy Clin. Immunol. 2017;139:S65–S76. doi: 10.1016/j.jaci.2017.01.011. PubMed DOI PMC

Hamilton J.D., Suárez-Fariñas M., Dhingra N., Cardinale I., Li X., Kostic A., Ming J.E., Radin A.R., Krueger J.G., Graham N., et al. Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis. J. Allergy Clin. Immunol. 2014;134:1293–1300. doi: 10.1016/j.jaci.2014.10.013. PubMed DOI

Sehra S., Yao Y., Howell M.D., Nguyen E.T., Kansas G.S., Leung D.Y.M., Travers J.B., Kaplan M.H. IL-4 Regulates Skin Homeostasis and the Predisposition toward Allergic Skin Inflammation. J. Immunol. 2010;184:3186–3190. doi: 10.4049/jimmunol.0901860. PubMed DOI PMC

Coussens L.M., Werb Z. Inflammation and cancer. Nature. 2002;420:860–867. doi: 10.1038/nature01322. PubMed DOI PMC

Dolcetti L., Peranzoni E., Ugel S., Marigo I., Fernandez Gomez A., Mesa C., Geilich M., Winkels G., Traggiai E., Casati A., et al. Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur. J. Immunol. 2009;40:22–35. doi: 10.1002/eji.200939903. PubMed DOI

Gerada C., Ryan K.M. Autophagy, the innate immune response and cancer. Mol. Oncol. 2020;14:1913–1929. doi: 10.1002/1878-0261.12774. PubMed DOI PMC

Global Interactome Mapping Reveals Pro-tumorigenic Interactions of NF-κB in Breast Cancer