EVALUATION ONE MOLECULAR EFFECT OF NEISSERIA GONORRHOEAE LIPOOLIGOSACHARIDE TOXICITY IN MICE SPLEEN, BASED ON ACTIVATION OF UNFOLDED PROTEIN RESPONSE THROUGH INOSITOL REQUIRING ENZYME-1Α

Background and Aim:It is confirmed that long term exposure to bacterial endotoxins, Lipopolysacharide (LPS) or lipooligosacharide (LOS), are one of the key factors result in multi -organ failure along with sepsis and septic shock. Despite wide studies on Neisseriameningitidis endotoxin (LOS), no remarkable study has been conducted due to Neisseria gonorrhoeae endotoxin (LOS). The unfolded protein response (UPR) is a cytoprotective response in the endoplasmic reticulum (ER) that promotes cell repair and sustain surveillance by reducing the load of unfolded/missfolded proteins and restores homeostasis following stress condition on ER, which induce innate immune signaling in response to invading microorganisms. Neisseria gonorrhoeae LOS, is a pathogen- associatedmolecular pattern (PAMP) in which, activates ER stress signal transduction through UPR. Among Three UPR stress sensors, Inositol requiring enzyme-1α (IRE-1α) conducts the most conservative signaling. pathway.Methods:N. gonorrhoeae lipooligosacharide was extracted using specific extraction kit. Intraperitoneally (IP) injected C57BL/6 male mice were ethically sacrificed and their spleen removed after 2, 8 and 24 hours after treatment.Considering aseptic-RNase free condition, Extracted RNA from removed spleen was applied for. cDNA synthesis After Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), the unfolded protein response pathway through IRE-1 stress sensor activation was evaluated via agarose gel electrophoretic pattern.Results:Treatment of mice with LOS and LPS (3 mg/kg) result in activation of UPR through IRE-1 pathway in order to spliced/unspliced X-box binding protein-1 (XBP-1) mRNA gene.Conclusion:This study can drop a knowledge and alternative pathway through N.gonorrhoeae pathogenicity mechanism, therapeutic pathway, and a future glance in counteracting with sepsis and septic shock.

کلیدواژه ها:

Neisseria gonorrhoeae ، lipopolysacharide (LPS) ، lipooligosacharide (LOS) ، unfolded protein response (UPR) ، inositol requiring enzyme-1 (IRE-1) ، X-box Binding Protein-1 (XBP-1)