دورية أكاديمية
أعرض في EDS

High Glucose Promotes Inflammation and Weakens Placental Defenses against E. coli and S. agalactiae Infection: Protective Role of Insulin and Metformin.

التفاصيل البيبلوغرافية
العنوان: High Glucose Promotes Inflammation and Weakens Placental Defenses against E. coli and S. agalactiae Infection: Protective Role of Insulin and Metformin.
المؤلفون: Jiménez-Escutia R; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico.; Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico., Vargas-Alcantar D; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico.; Posgrado en Ciencias de la Salud, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Flores-Espinosa P; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico., Helguera-Repetto AC; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico., Villavicencio-Carrisoza O; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico., Mancilla-Herrera I; Departamento de Infectología e Inmunología, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico., Irles C; INSERM, UMR 978, Université Sorbonne Paris Nord, UFR SMBH, 93017 Bobigny, France., Torres-Ramos YD; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico., Valdespino-Vazquez MY; Departamento de Patología, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico., Velázquez-Sánchez P; Departamento de Ginecología y Obstetricia, Hospital Ángeles México, Mexico City 11800, Mexico., Zamora-Escudero R; Ginecología y Obstetricia, Hospital Ángeles Lomas-UNAM, Huixquilucan 52763, Mexico., Islas-López M; Ginecología y Obstetricia, Hospital Ángeles Lomas-UNAM, Huixquilucan 52763, Mexico., Carranco-Salinas C; División de Obstetricia, Hospital de Ginecología y Obstetricia No. 4, IMSS, Mexico City 01090, Mexico., Díaz L; Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico., Zaga-Clavellina V; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico., Olmos-Ortiz A; Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Mexico City 11000, Mexico.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2023 Mar 09; Vol. 24 (6). Date of Electronic Publication: 2023 Mar 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: beta-Defensins*/metabolism , Diabetes, Gestational*/metabolism , Hyperglycemia*/metabolism , Metformin*/pharmacology , Metformin*/therapeutic use , Metformin*/metabolism, Female ; Humans ; Pregnancy ; Escherichia coli/metabolism ; Glucose/metabolism ; Inflammation/metabolism ; Insulin/metabolism ; Insulin, Regular, Human/pharmacology ; Placenta/metabolism ; Streptococcus agalactiae/metabolism
مستخلص: Placentas from gestational diabetes mellitus (GDM) patients undergo significant metabolic and immunologic adaptations due to hyperglycemia, which results in an exacerbated synthesis of proinflammatory cytokines and an increased risk for infections. Insulin or metformin are clinically indicated for the treatment of GDM; however, there is limited information about the immunomodulatory activity of these drugs in the human placenta, especially in the context of maternal infections. Our objective was to study the role of insulin and metformin in the placental inflammatory response and innate defense against common etiopathological agents of pregnancy bacterial infections, such as E. coli and S. agalactiae , in a hyperglycemic environment. Term placental explants were cultivated with glucose (10 and 50 mM), insulin (50-500 nM) or metformin (125-500 µM) for 48 h, and then they were challenged with live bacteria (1 × 10 5 CFU/mL). We evaluated the inflammatory cytokine secretion, beta defensins production, bacterial count and bacterial tissue invasiveness after 4-8 h of infection. Our results showed that a GDM-associated hyperglycemic environment induced an inflammatory response and a decreased beta defensins synthesis unable to restrain bacterial infection. Notably, both insulin and metformin exerted anti-inflammatory effects under hyperglycemic infectious and non-infectious scenarios. Moreover, both drugs fortified placental barrier defenses, resulting in reduced E. coli counts, as well as decreased S. agalactiae and E. coli invasiveness of placental villous trees. Remarkably, the double challenge of high glucose and infection provoked a pathogen-specific attenuated placental inflammatory response in the hyperglycemic condition, mainly denoted by reduced TNF-α and IL-6 secretion after S. agalactiae infection and by IL-1β after E. coli infection. Altogether, these results suggest that metabolically uncontrolled GDM mothers develop diverse immune placental alterations, which may help to explain their increased vulnerability to bacterial pathogens.
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معلومات مُعتمدة: CB-A1-S-27832 Consejo Nacional de Ciencia y Tecnología; 2018-1-152 Instituto Nacional de Perinatología
فهرسة مساهمة: Keywords: bacterial count; bacterial invasiveness; cytokine tolerization; human term placenta; hyperglycemia; hypoglycemics; inflammatory cytokines
المشرفين على المادة: 0 (beta-Defensins)
IY9XDZ35W2 (Glucose)
0 (Insulin)
0 (Insulin, Regular, Human)
9100L32L2N (Metformin)
تواريخ الأحداث: Date Created: 20230329 Date Completed: 20230330 Latest Revision: 20230405
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10048930
DOI: 10.3390/ijms24065243
PMID: 36982317
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms24065243