title: Expression and functional characterization of NOD2 in decidual stromal cells isolated during the first trimester of pregnancy.
abstract: NOD2, one of the cytosolic proteins that contain a nuclear oligomerization domain (NOD), is a pattern recognition receptor (PRR) involved in innate immune responses to intracellular pathogens. Little is known, however, about the effect of NOD2 expression on the maternal-fetal relationship. Our aim was to elucidate the functions of NOD2 in normal decidual stromal cells (DSCs) from the first trimester. Tissues and DSCs were isolated from 26 patients with normal pregnancies that required abortion. The expression of NOD2 in deciduas/decidual stromal cells (DSCs) was examined by real-time PCR, immunohistochemistry, and In-cell western. DSCs containing NOD2 were stimulated by its ligand, muramyl dipeptide (MDP). The secretion of various cytokines and chemokines were measured by ELISA and the apoptotic rate was determined by flow cytometry. Treatment with MDP significantly elevated the expression of both NOD2 mRNA and protein levels in DSCs. In addition, MDP activation of NOD2 significantly increased IL-1β and MCP-1 cytokine expression in a dose dependent manner but had no effect on IL-12 expression. IL-1β and TNF-α also significantly increased the expression of NOD2 in DSCs, suggesting a positive feedback loop mechanism. Moreover, MDP stimulation augmented DSC apoptosis. In summary, the results suggest that NOD2 expression in DSCs plays an important role in protecting the embryo and preventing infection in the maternal-fetal interface.
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hua-zhao
authors.initials: HZ
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, China.
authors.forename: Mei-lan
authors.initials: ML
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, The first Hospital of JiLin University, Changchun, China.
authors.forename: Yi-yang
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiao-lu
authors.initials: XL
authors.lastname: Nie
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Du
authors.affiliation: Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Da-jin
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Zhang
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000328:Adult; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003656:Decidua / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D025461:Feedback, Physiological; D005260:Female; D005315:Fetal Diseases / Q000517:prevention & control; D016905:Gram-Negative Bacterial Infections / Q000517:prevention & control / Q000635:transmission; D016908:Gram-Positive Bacterial Infections / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008431:Maternal-Fetal Exchange / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists / Q000032:analysis / Q000502:physiology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000276:immunology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C440499:lipopolysaccharide, Escherichia coli O111 B4; D000119:Acetylmuramyl-Alanyl-Isoglutamine