Tang, XiaorenDibart, SergeElgreu , Thuraya Nuri2025-07-302025-07-302025https://hdl.handle.net/2144/507782025OBJECTIVE: It is known that Lipopolysaccharide derived from gram-negative bacteria induces initiation and progression of periodontal disease via factors such as NF-κB, TNF-α, IL-1β, and CXCL1. Down -regulation of these inflammatory mediators induced by periodontal bacteria through inhibitors may result in inhibition or resolution of inflammation and subsequent disease. Preliminary data indicated that Porphyromonas gingivalis (P. gingivalis ) / lipopolysaccharide (LPS) stimulates CXCL1 production in macrophages. The expression of CXCL1 increases inflammation and inflammatory diseases. However, little is known about the mechanism by which CXCL1 is related to different diseases. We studied the biological function of CXCL1, examined shRNAs as inhibitors, and identified whether the suppression of CXCL1 leads to reduced LPS-induced TNF-α production. We have also reviewed and analyzed the data of some periodontal pathogenic bacteria and its related systemic diseases. We also reviewed the latest research on inhibitors against inflammation that have potential to be further applied clinically. MATERIALS AND METHODS: Recombinant plasmid DNA with human CXCL1 cDNA were cloned and transfected into human THP-1 monocyte-like cells. They were then treated with different inhibitors and TNF-α and IL-1β production were measured via ELISA. In addition, several CXCL1 siRNAs were designed, synthesized and tested as inhibitors. The specificity of CXCL1 siRNA inhibition of LPS-induced proteins was analyzed using ELISA and our hybrid method analysis. We analyzed oral bacteria (P. gingivalis, T. denticola, T. forsythia, A. actinomycetemcomitans, and F. nucleatum) produced by treatments and mediators using western blot, and ELISA. RESULTS: Our data showed that the treatment of cells with a Janus kinase (JAK) inhibitor or CXCL1 siRNA#2 suppresses CXCL1 gene expression and reduces TNF-α production in response to LPS. SiRNA#2 also led to significant inhibition of LPS-induced pro-inflammatory chemokines, kinases, transcriptional factors, and apoptotic gene. CONCLUSIONS: This is a promising study regarding the mechanism of CXCL1 in the LPS-dependent pathway. CXCL1 is involved in the LPS-induced proinflammatory cytokine production through JAK signaling pathway. We demonstrated that CXCL1 siRNA effectively inhibits CXCL1 and LPS-induced pro-inflammatory cytokines, chemokines, kinases, transcriptional factors, and apoptotic gene.en-USDentistryImmunologyBiologyThesis/Dissertation2025-07-290000-0002-8884-443X