KEITH KIRKWOOD DDS, PhD personal profile
Periodontal disease progression is a consequence of the host immune inflammatory response to oral pathogens. Sexual dimorphism is evident in the innate immune system where lipopolysaccharide (LPS) derived from periodontal pathogens stimulates the production of cytokines and chemokines in a more robust manner in males compared to females contributing towards increase susceptibility of periodontal disease in males. The role of p38/MKP-1 signaling in chronic inflammation and periodontal disease progression supports the concept that MKP-1 signaling is vital to attenuate MAPK-induced innate immune cytokine expression at the post-transcriptional level through mRNA interaction with RNA binding proteins. In vivo models in periodontal and periapical bone loss indicate that in the absence of MKP-1, there is enhanced neutrophil infiltrate and inflammation in a sex-dependent manner. Based upon these data, we have ongoing studies that address the role of MKP-1 in regulating cytokine/chemokine production in activated neutrophil trafficking, chemokine signaling, and chemokine/cytokine gene regulation during periodontal disease progression contributing to the sexual dimorphism of the innate immune response observed in periodontitis. We utilize cutting edge techniques to address the role of MKP-1 in neutrophil function including magnetic cell sorting, flow cytometry, real time gene expression, and Nanostring gene expression techniques.