The increasing aging population and aging-associated diseases have become a global issue for decades.People over 65 show an increased prevalence and greater severity of periodontitis,which poses threats to overall hea...The increasing aging population and aging-associated diseases have become a global issue for decades.People over 65 show an increased prevalence and greater severity of periodontitis,which poses threats to overall health.Studies have demonstrated a significant association between aging and the dysfunction of neutrophils,critical cells in the early stages of periodontitis,and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion.Neutrophils differentiate and mature in the bone marrow before entering the circulation;during an infection,they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens.Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues.The impacts of aging on neutrophils'chemotaxis,anti-microbial function,cell activation,and lifespan result in impaired neutrophil functions and excessive neutrophil activation,which could influence periodontitis course.We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses.We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging.This review could help us better understand the pathogenesis of periodontitis,which could offer novel therapeutic targets for periodontitis.展开更多
Although sympathetic blockade is clinically used to treat pain,the underlying mechanisms remain unclear.We developed a localized microsympathectomy(mSYMPX),by cutting the grey rami entering the spinal nerves near the ...Although sympathetic blockade is clinically used to treat pain,the underlying mechanisms remain unclear.We developed a localized microsympathectomy(mSYMPX),by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia(DRG).In a chemotherapy-induced peripheral neuropathy model,mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β(TGF-β)and its receptor TGF-βR1.Here,we examined the role of TGF-βin sympathetic-mediated radiculopathy produced by local inflammation of the DRG(LID).Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID.Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1.Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity,and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX.In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages,and Tgfbr1 in neurons.We suggest that TGF-βsignaling is a general underlying mechanism of local sympathetic blockade.展开更多
文摘The increasing aging population and aging-associated diseases have become a global issue for decades.People over 65 show an increased prevalence and greater severity of periodontitis,which poses threats to overall health.Studies have demonstrated a significant association between aging and the dysfunction of neutrophils,critical cells in the early stages of periodontitis,and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion.Neutrophils differentiate and mature in the bone marrow before entering the circulation;during an infection,they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens.Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues.The impacts of aging on neutrophils'chemotaxis,anti-microbial function,cell activation,and lifespan result in impaired neutrophil functions and excessive neutrophil activation,which could influence periodontitis course.We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses.We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging.This review could help us better understand the pathogenesis of periodontitis,which could offer novel therapeutic targets for periodontitis.
基金This work was supported by NIH Grants NS045594 and NS113243.
文摘Although sympathetic blockade is clinically used to treat pain,the underlying mechanisms remain unclear.We developed a localized microsympathectomy(mSYMPX),by cutting the grey rami entering the spinal nerves near the rodent lumbar dorsal root ganglia(DRG).In a chemotherapy-induced peripheral neuropathy model,mSYMPX attenuated pain behaviors via DRG macrophages and the anti-inflammatory actions of transforming growth factor-β(TGF-β)and its receptor TGF-βR1.Here,we examined the role of TGF-βin sympathetic-mediated radiculopathy produced by local inflammation of the DRG(LID).Mice showed mechanical hypersensitivity and transcriptional and protein upregulation of TGF-β1 and TGF-βR1 three days after LID.Microsympathectomy prevented mechanical hypersensitivity and further upregulated Tgfb1 and Tgfbr1.Intrathecal delivery of TGF-β1 rapidly relieved the LID-induced mechanical hypersensitivity,and TGF-βR1 antagonists rapidly unmasked the mechanical hypersensitivity after LID+mSYMPX.In situ hybridization showed that Tgfb1 was largely expressed in DRG macrophages,and Tgfbr1 in neurons.We suggest that TGF-βsignaling is a general underlying mechanism of local sympathetic blockade.
