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Intracellular Receptors and Gonococcal Induction of Proinflammatory

细胞内受体和淋菌诱导的促炎症

基本信息

批准号：
7764291
负责人：
Caroline A Genco
金额：
$ 36.77万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-25 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7764291
关键词：
Animals Automobile Driving Binding Bone Marrow Breeding Cell physiology Cells Cytokine Activation Disease Embryo Epithelial Cells Genital system Gonorrhea Human Immune Immune response Immunity Immunologic Receptors In Vitro Infection Inflammation Inflammatory Inflammatory Response Interleukin-6 Interleukins Kidney Knockout Mice Knowledge Laboratories Life Ligands Mammalian Oviducts Mediator of activation protein Modeling Mus Neisseria Neisseria gonorrhoeae Nucleotides Pathology Pattern Pattern recognition receptor Phagocytes Production Protein-Serine-Threonine Kinases Proteins Receptor Signaling Receptor-Interacting Serine/Threonine Protein Kinase 2 Role Sexually Transmitted Diseases Signal Transduction System TLR2 gene TLR4 gene Testing Toll-like receptors Tumor Necrosis Factor-alpha Tumor Necrosis Factors base chemokine cytokine improved in vivo inhibitor-of-apoptosis protein macrophage mouse model novel pathogen receptor reproductive response

项目摘要

Proinflammatory cytokines are expressed in vivo during infection with the sexually transmitted disease pathogen Neisseria gonorrhoeae and contribute to disease pathology. The activation of proinflammatory cytokines is directed by pattern recognifion receptors (PRRs). PRRs can be classified as transmembrane molecules such at the Toll-like receptors (TLRs), or cytosolic molecules including Nod- like receptors (NLRs). TLR2 and TLR4 funcfion as receptors for Neisseria ligands. However, nothing is known about cytosolic molecules that respond to intracellular N. gonorrhoeae. We recently demonstrated that blocking signaling through TLRs using antagonisfic anfibodies only partially reduced the producfion of proinflammatory cytokines following N. gonorrhoeae infection of epithelial cells suggesfing that intracellular NLRs may be employed for N. gonorrhoeae induced proinflammatory cytokines. We also demonstrated that infection of epithelial cells with N. gonorrhoeae induced the expression of NLRs including Nodi and a protein recently implicated in intracellular immune recognifion, inhibitor of apoptosis protein (clAP-2), as well as the receptorinteracfing serine-threonine kinase 2 (R1P2), a key mediator of innate immune signaling. Furthermore, we established that N. gonorrhoeae sfimulates proinflammatory cytokine responses through Nodi and Nod 2 in an over expression system. Based on these observafions we propose that N. gonorrhoeae employs specific intracellular signaling receptors that respond to intracellular gonococci and or their ligands, resulfing in proinflammatory responses that contribute to N. gonorrhoeae induced inflammation in vivo. To test this hypothesis we propose the following aims: 1. To define the role of NLR signaling receptors (clAP2, N0D1, and N0D2) in N. gonorrhoeae inducfion of proinfiammatory cytokines in human epithelial cells and macrophages; 2. To define the role of NLR signaling receptors (clAP2, N0D1, and N0D2) in N. gonorrhoeae induction of proinflammatory cytokines in murine epithelial cells and macrophages; and 3. To define the role of NLRs in N. gonorrhoeae induced infiammatory responses in a mouse model.

促炎细胞因子在性传播疾病感染期间在体内表达