RESUMO
Pedicle screw instrumentation has become standard fixation for a variety of spinal disorders. Traditionally, the landmarks for screw insertion have been described as the junction of the pars interarticularis, with the superior articular process of the corresponding facet and the transverse process. Consistent and reproducible insertion remains challenging specifically when faced with anatomic patient variations and superimposed pathology. We describe a novel method to approach pedicle screw fixation using primarily the transverse process.
Assuntos
Parafusos Ósseos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Humanos , Fusão Vertebral/instrumentaçãoRESUMO
BACKGROUND: IL-4 and signal transducer and activator of transcription 6 (STAT6) play an important role in the progression of allergic airway disease (AAD) or asthma. IL-4 and STAT6 mediate T(H)2 responses in T cells and immunoglobulin class-switching to IgE in B cells. Both T(H)2 responses and IgE promote the asthmatic condition. We have previously demonstrated that poly (ADP-ribose) polymerase (PARP) 14, a member of the PARP family of proteins, regulates the transcription function of STAT6. However, the role of PARP-14 in AAD is not known. OBJECTIVE: Here we investigate the role of PARP-14 and the enzyme activity associated with it in a model of AAD dependent on airway hyperresponsiveness and lung inflammation. We also elucidate the mechanism by which PARP-14 regulates AAD. METHODS: The role of PARP-14 and its enzyme activity in AAD and T(H)2 differentiation were examined by using a murine model of AAD and in vitro T(H) cell differentiation. RESULTS: PARP-14-deficient animals show reduced lung pathology and IgE levels when compared with control animals. Treating mice with a pharmacologic inhibitor for PARP activity reduced the severity of airway hyperresponsiveness and lung inflammation. Mechanistically, our data indicate that PARP-14 and its enzyme activity aid in the differentiation of T cells toward a T(H)2 phenotype by regulating the binding of STAT6 to the Gata3 promoter. CONCLUSION: PARP-14 and the catalytic activity associated with it promote T(H)2 differentiation and AAD in a murine model, and targeting PARP-14 might be a potential new therapy for allergic asthma.
Assuntos
Hiper-Reatividade Brônquica/patologia , Hipersensibilidade/patologia , Poli(ADP-Ribose) Polimerases/metabolismo , Doenças Respiratórias/patologia , Células Th2/enzimologia , Células Th2/patologia , Animais , Asma/genética , Asma/metabolismo , Asma/patologia , Hiper-Reatividade Brônquica/enzimologia , Hiper-Reatividade Brônquica/genética , Hiper-Reatividade Brônquica/metabolismo , Diferenciação Celular/imunologia , Células Cultivadas , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Hipersensibilidade/genética , Hipersensibilidade/metabolismo , Imunoglobulina E/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/imunologia , Regiões Promotoras Genéticas/genética , Doenças Respiratórias/enzimologia , Doenças Respiratórias/genética , Doenças Respiratórias/metabolismo , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Células Th2/metabolismoRESUMO
A model of Staphylococcus aureus-induced pneumonia in adult, immunocompetent C57BL/6J mice is described. This model closely mimics the clinical and pathological features of pneumonia in human patients. Using this system, we defined a role for S. aureus strain Newman surface proteins and secreted exotoxins in pneumonia-related mortality.
