Role Of Progesterone And Lipooligosacharide In The Pathogenic Mechanisms Of Neisseria Gonorrhoeae

Objective:To investigate the effect of progesterone on Neisseria gonorrhoeae-i nduced activation of NLRP3 inflammasome.Methods:Construction of ovariectomized and normal gonococcal infection model.20 balb/c mice were randomly divided into 4 groups. Group 1:sham+gonococcal infection group (intact). Group2:Ovariectomized+ gonococcal infection group. Group 3:Ovariectomized+gonococcal infection+ progesterone (1 mg/d). Group 4:sham operation+saline group (control). We detected the CFU of daily vaginal discharge after inoculation, quantity of infiltration neutrophils and expression levels of IL-1?, TNF-a and IL-6 in vagina. HE staining was employed for histopathology study of vagina and cervix and immunofluorescence for NLRP3 and caspase 1-p20 expression levels. In vitro study, cells were divided into five groups:THP-1 cells (control) group; THP-1+ Neisseria gonorrhoeae NG; THP-1 cells+gonorrhoeae+10 ng/mL P4 (NG +10 ng/mL P4) group cells; 4. THP-1 gonorrhoeae+100 ng/mL P4 (NG+100 ng/ mL P4); 5. THP-1 cells+Neisseria gonorrhoeae+1000 ng/ml P4 (NG+1000 ng/ mL P4). ELISA assay were used to detect the IL-1? levels which was secreted by THP-1 cell, western-blot assay to detect the intracellular NLRP3, caspase-1 and NF-kB expression. Also we utilized RT-PCR for intracellular IL-10 and NF-kB mRNA detection and the fluorescence probe for ROS test.Results:(1) In vivo study, progesterone was demonstrated to decrease the amount of Neisseria gonorrhoeae in vigina and cervix of mice, ameliorating induced infiltration of inflammatory cells while expression of IL-1?, TNF-a and IL-6 was also decreased; (2) In vitro study we confirmed that progesterone inhibited activation of NLRP3, caspase-1 and NF-kB, decreasing the expression of IL-1? and ROS.Conclusion:progesterone was demonstrated to inhibit Neisseria gonorrhoeae induced activation of NLRP3 via suppression of NF-kB and ROS production, contributing to reduced infiltration of inflammatory cells and decreased inflammatory factors like IL-1?, TNF-a and IL-6 in Neisseria gonorrhoeae infected vagina and cervix tissues. This study elaborates the pathogenic mechanism of asymptomatic gonorrhea infection from another perspective, which provides a new strategy for prevention and treatment of gonorrhea.