{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T07:24:53Z","timestamp":1774682693993,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T00:00:00Z","timestamp":1529366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Program for Changjiang Scholars and Innovative Research Team in University","award":["[PCSIRT, No. IRT_14R41]"],"award-info":[{"award-number":["[PCSIRT, No. IRT_14R41]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cutaneous eruption is a common drug-adverse reaction, characterised by keratinocytes inflammation and apoptosis. Shuanghuanglian injeciton (SHLI) is a typical Chinese medicine injection, which is used to treat influenza. It has been reported that SHLI has the potential to induce cutaneous adverse eruptions. However, the mechanisms remain unclear. Since desmoglein 1 (DSG1) shows a crucial role in maintaining skin barrier function and cell susceptibility, we assume that DSG1 plays a critical role in the cutaneous eruptions induced by SHLI. In our study, retinoic acid (RA) was selected to downregulate the DSG1 expression, and lipopolysaccharide (LPS) was first used to identify the susceptibility of the DSG1-deficiency Hacat cells. Then, SHLI was administrated to normal or DSG1-deficient Hacat cells and mice. The inflammatory factors and apoptosis rate were evaluated by RT-PCR and flow cytometry. The skin pathological morphology was observed by hematoxylin and eosin (HE) staining. Our results show that treated only with SHLI could not cause IL-4 and TNF-\u03b1 mRNA increases in normal Hacat cells. However, in the DSG1-deficient Hacat cells or mice, SHLI induced an extreme increase of IL-4 and TNF-\u03b1 mRNA levels, as well as in the apoptosis rate. The skin tissue showed a local inflammatory cell infiltration when treated with SHIL in the DSG1-deficient mice. Thus, we concluded that DSG1 deficiency was a potential causation of SHLI induced eruptions. These results indicated that keratinocytes with DSG1 deficiency were likely to induce the cutaneous eruptions when stimulated with other medicines.<\/jats:p>","DOI":"10.3390\/molecules23061477","type":"journal-article","created":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T11:20:36Z","timestamp":1529407236000},"page":"1477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Desmoglein1 Deficiency Is a Potential Cause of Cutaneous Eruptions Induced by Shuanghuanglian Injection"],"prefix":"10.3390","volume":"23","author":[{"given":"Yidan","family":"Zhang","sequence":"first","affiliation":[{"name":"Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiujun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Academy of Traditional Chinese Medicine, Tianjin 300120, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanshan","family":"Fan","sequence":"additional","affiliation":[{"name":"Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Song","sequence":"additional","affiliation":[{"name":"Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[{"name":"Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2624-683X","authenticated-orcid":false,"given":"Pengwei","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"},{"name":"Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"},{"name":"Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.tox.2003.09.004","article-title":"Drug Hypersensitivity Reactions in Skin: Understanding Mechanisms and the Development of Diagnostic and Predictive Tests","volume":"194","author":"Naisbitt","year":"2004","journal-title":"Toxicology"},{"key":"ref_2","first-page":"256","article-title":"Cutaneous Adverse Drug Reactions","volume":"36","year":"2015","journal-title":"Rev. Med. Interne"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1056\/NEJM199411103311906","article-title":"Severe Adverse Cutaneous Reactions to Drugs","volume":"331","author":"Roujeau","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.taap.2014.08.019","article-title":"Keratinocyte-Derived Il-24 Plays a Role in the Positive Feedback Regulation of Epidermal Inflammation in Response to Environmental and Endogenous Toxic Stressors","volume":"280","author":"Jin","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.jaci.2012.02.020","article-title":"Mechanisms of Ifn-Gamma-Induced Apoptosis of Human Skin Keratinocytes in Patients with Atopic Dermatitis","volume":"129","author":"Rebane","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","first-page":"899","article-title":"Role of the Epidermal Barrier in Atopic Dermatitis","volume":"7","author":"Proksch","year":"2009","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_7","first-page":"95","article-title":"The Role of Impaired Epidermal Barrier Function in Atopic Dermatitis","volume":"24","author":"Marinovic","year":"2016","journal-title":"Acta Dermatovenerol. Croat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0955-0674(02)00366-6","article-title":"Desmosomal Cadherins","volume":"14","author":"Garrod","year":"2002","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3109\/15419061.2013.876018","article-title":"Desmosomal Adhesion in Vivo","volume":"21","author":"Berika","year":"2014","journal-title":"Cell Commun. Adhes."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1083\/jcb.153.2.243","article-title":"Desmoglein Isoform Distribution Affects Stratum Corneum Structure and Function","volume":"153","author":"Elias","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"524","DOI":"10.2183\/pjab.86.524","article-title":"Autoimmune and Infectious Skin Diseases That Target Desmogleins","volume":"86","author":"Amagai","year":"2010","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1083\/jcb.200809044","article-title":"Desmoglein 1-Dependent Suppression of Egfr Signaling Promotes Epidermal Differentiation and Morphogenesis","volume":"185","author":"Getsios","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.bbamem.2007.07.014","article-title":"Desmosome Structure, Composition and Function","volume":"1778","author":"Garrod","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/ng.2739","article-title":"Desmoglein 1 Deficiency Results in Severe Dermatitis, Multiple Allergies and Metabolic Wasting","volume":"45","author":"Samuelov","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fcimb.2018.00010","article-title":"Streptococcal Cysteine Protease-Mediated Cleavage of Desmogleins Is Involved in the Pathogenesis of Cutaneous Infection","volume":"8","author":"Sumitomo","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"439","DOI":"10.5021\/ad.2011.23.4.439","article-title":"Retinoid Induces the Degradation of Corneodesmosomes and Downregulation of Corneodesmosomal Cadherins: Implications on the Mechanism of Retinoid-Induced Desquamation","volume":"23","author":"Kim","year":"2011","journal-title":"Ann. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1002\/jssc.201500712","article-title":"High-Performance Liquid Chromatography with Photodiode Array Detection and Chemometrics Method for the Analysis of Multiple Components in the Traditional Chinese Medicine Shuanghuanglian Oral Liquid","volume":"38","author":"Li","year":"2015","journal-title":"J. Sep. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1756-5391.2010.01067.x","article-title":"Adverse Drug Reactions of Shuanghuanglian Injection: A Systematic Review of Public Literatures","volume":"3","author":"Wang","year":"2010","journal-title":"J. Evid.-Based Med."},{"key":"ref_19","first-page":"2723","article-title":"Influence of Solvent and Drug Preparation Time on Shuanghuanglian Injections Induce Pseudo-Allergic Reaction","volume":"40","author":"Yi","year":"2015","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_20","first-page":"2727","article-title":"Study of Screening Pseudoallergenic Substances of Shuanghuanglian Injection","volume":"40","author":"Yi","year":"2015","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jim.2004.06.022","article-title":"Label-Free, Real-Time Monitoring of Ige-Mediated Mast Cell Activation on Microelectronic Cell Sensor Arrays","volume":"292","author":"Abassi","year":"2004","journal-title":"J. Immunol. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.acthis.2014.01.009","article-title":"Retinoic Acid Induced Repair in the Lung of Adult Hyperoxic Mice, Reducing Transforming Growth Factor-Beta1 (Tgf-Beta1) Mediated Abnormal Alterations","volume":"116","author":"Kayalar","year":"2014","journal-title":"Acta Histochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1097\/ACI.0b013e328355b865","article-title":"Immunological Mechanisms of Epidermal Damage in Toxic Epidermal Necrolysis","volume":"12","author":"Tohyama","year":"2012","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1034\/j.1600-0625.2001.010002090.x","article-title":"Characterization of the Desmosomal Cadherin Gene Family: Genomic Organization of Two Desmoglein Genes on Human Chromosome 18q12","volume":"10","author":"Frank","year":"2001","journal-title":"Exp. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1067\/mai.2002.120563","article-title":"Delayed Reactions to Drugs Show Levels of Perforin, Granzyme B, and Fas-L to Be Related to Disease Severity","volume":"109","author":"Posadas","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/00000372-200010000-00005","article-title":"Immunoregulatory Effector Cells in Drug-Induced Toxic Epidermal Necrolysis","volume":"22","author":"Paquet","year":"2000","journal-title":"Am. J. Dermatopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1067\/mjd.2002.120473","article-title":"Increased Interleukin 10, Tumor Necrosis Factor Alpha, and Interleukin 6 Levels in Blister Fluid of Toxic Epidermal Necrolysis","volume":"47","author":"Correia","year":"2002","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1111\/j.0022-202X.2004.23439.x","article-title":"Evaluation of the Potential Role of Cytokines in Toxic Epidermal Necrolysis","volume":"123","author":"Nassif","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jaci.2004.04.034","article-title":"Involvement of Ccl27-Ccr10 Interactions in Drug-Induced Cutaneous Reactions","volume":"114","author":"Tapia","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1111\/j.1365-2133.2006.07398.x","article-title":"Expression of Cytokines and Chemokine Receptors in the Cutaneous Lesions of Erythema Multiforme and Stevens-Johnson Syndrome\/Toxic Epidermal Necrolysis","volume":"155","author":"Caproni","year":"2006","journal-title":"Br. J. Dermatol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/6\/1477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:09:10Z","timestamp":1760195350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/6\/1477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,19]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,6]]}},"alternative-id":["molecules23061477"],"URL":"https:\/\/doi.org\/10.3390\/molecules23061477","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,19]]}}}