Sugar signaling is a mechanism that plants use to integrate various internal and external cues to achieve nutrient homeostasis, mediate developmental programs, and articulate stress responses. Many bZlP transcription ...Sugar signaling is a mechanism that plants use to integrate various internal and external cues to achieve nutrient homeostasis, mediate developmental programs, and articulate stress responses. Many bZlP transcription factors are known to be involved in nutrient and/or stress signaling. An Arabidopsis Sl-group bZlP gene, AtbZIP1, was identified as a sugar-sensitive gene in a previous gene expression profiling study （Plant Cell. 16, 2128-2150）. In this report, we show that the expression of AtbZIP1 is repressed by sugars in a fast, sensitive, and reversible way. The sugar repression of Atb- ZIP1 is affected by a conserved sugar signaling component, hexokinase. Besides being a sugar-regulated gene, AtbZIP1 can mediate sugar signaling and affect gene expression, plant growth, and development. When carbon nutrients are limited, gain or loss of function of AtbZlP1 causes changes in the rates of early seedling establishment. Results of phenotypic analyses indicate that AtbZlP1 acts as a negative regulator of early seedling growth. Using gain- and loss-of-function plants in a microarray analysis, two sets of putative AtbZIP1-regulated genes have been identified. Among them, sugar-responsive genes are highly over-represented, implicating a role of AtbZlP1 in sugar-mediated gene expression. Using yeast two-hybrid （Y-2-H） screens and bimolecular fluorescence complementation （BiFC） analyses, we are able to recapitulate extensive C/S1 AtbZlP protein interacting network in living cells. Finally, we show that AtbZIP1 can bind ACGT-based motifs in vitro and that the binding characteristics appear to be affected by the heterodimerization between AtbZlP1 and the C-group AtbZIPs, including AtbZlP10 and AtbZlP63.展开更多
Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who a...Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.展开更多
"Practice is the hardest part of learning,and training is the essence of transformation."Ann Voskamp,One Thousand Gifts:A Dare to Live Fully Right Where YouAre Early-life exposure to environmental allergens ..."Practice is the hardest part of learning,and training is the essence of transformation."Ann Voskamp,One Thousand Gifts:A Dare to Live Fully Right Where YouAre Early-life exposure to environmental allergens and viral infections can lead to trained immunity and macrophage polarization resulting in an augmented type 2 immune response in allergic disorders.However,the detailed mechanism is unknown.展开更多
Virus-induced asthma is prevalent among children,but its underlying mechanisms are unclear.Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma.Nonethe...Virus-induced asthma is prevalent among children,but its underlying mechanisms are unclear.Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma.Nonetheless,the relationship between systemic virus infections,such as enterovirus infection,and the ensuing effects on allergic asthma development is unknown.Early-life enterovirus infection was correlated with higher risks of allergic diseases in children.Adult mice exhibited exacerbated mite allergen-induced airway inflammation following recovery from EV-A71 infection in the neonatal period.Bone marrow-derived macrophages(BMDMs)from recovered EV-A71-infected mice showed sustained innate immune memory(trained immunity)that could drive naïve T helper cells toward Th2 and Th17 cell differentiation when in contact with mites.Adoptive transfer of EV-A71-trained BMDMs induced augmented allergic inflammation in naïve recipient mice,which was inhibited by 2-deoxy-D-glucose(2-DG)pretreatment,suggesting that trained macrophages following enterovirus infection are crucial in the progression of allergic asthma later in life.展开更多
基金This work was supported by The National Science Foundation （IOB- 0543751 to J.C.J.）.We thank the Arabidopsis Biological Resource Center （Columbus, Ohio） for providing DNA clones and seeds, Dr Biao Ding formicroscopy facility, Dr Steven St Martin for microarray design and data analysis, Cyrus Hah for protoplast transient expression analysis, Drs John Finer and Michelle Jones for critical reading of the manuscript, and Joe Takayama for greenhouse support. No conflict of interest declared.
文摘Sugar signaling is a mechanism that plants use to integrate various internal and external cues to achieve nutrient homeostasis, mediate developmental programs, and articulate stress responses. Many bZlP transcription factors are known to be involved in nutrient and/or stress signaling. An Arabidopsis Sl-group bZlP gene, AtbZIP1, was identified as a sugar-sensitive gene in a previous gene expression profiling study （Plant Cell. 16, 2128-2150）. In this report, we show that the expression of AtbZIP1 is repressed by sugars in a fast, sensitive, and reversible way. The sugar repression of Atb- ZIP1 is affected by a conserved sugar signaling component, hexokinase. Besides being a sugar-regulated gene, AtbZIP1 can mediate sugar signaling and affect gene expression, plant growth, and development. When carbon nutrients are limited, gain or loss of function of AtbZlP1 causes changes in the rates of early seedling establishment. Results of phenotypic analyses indicate that AtbZlP1 acts as a negative regulator of early seedling growth. Using gain- and loss-of-function plants in a microarray analysis, two sets of putative AtbZIP1-regulated genes have been identified. Among them, sugar-responsive genes are highly over-represented, implicating a role of AtbZlP1 in sugar-mediated gene expression. Using yeast two-hybrid （Y-2-H） screens and bimolecular fluorescence complementation （BiFC） analyses, we are able to recapitulate extensive C/S1 AtbZlP protein interacting network in living cells. Finally, we show that AtbZIP1 can bind ACGT-based motifs in vitro and that the binding characteristics appear to be affected by the heterodimerization between AtbZlP1 and the C-group AtbZIPs, including AtbZlP10 and AtbZlP63.
基金supported by the Ministry of Science and Technology(MOST)of Taiwan(grant numbers 103-2321-B-006-030 and 104-2321-B-006-008),funding received in part from the Headquarters of University Advancement at the National Cheng Kung University,which is sponsored by the Ministry of Education in Taiwan,and a research grant(1JA8)from the Center for Allergy,Immunology,and Microbiome(A.I.M.),China Medical University Hospital,Taichung,Taiwan.
文摘Increased levels of surfactant protein D (SP-D) and lipid-laden foamy macrophages (FMs) are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease (COPD) who are also chronically exposed to cigarette smoke (CS). However, the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined. In this study, increased levels of SP-D were found in the bronchoalveolar lavage fluid (BALF) and sera of ozone- and CS-exposed mice. Furthermore, SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure, similar to that exhibited by our study cohort of chronic smokers and COPD patients. We also showed that an exogenous recombinant fragment of human SP-D (rfhSP-D) prevented the formation of oxidized low-density lipoprotein (oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo. SP-D upregulated bone marrow-derived macrophage (BMDM) expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL. Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema, which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.
文摘"Practice is the hardest part of learning,and training is the essence of transformation."Ann Voskamp,One Thousand Gifts:A Dare to Live Fully Right Where YouAre Early-life exposure to environmental allergens and viral infections can lead to trained immunity and macrophage polarization resulting in an augmented type 2 immune response in allergic disorders.However,the detailed mechanism is unknown.
基金This study was,in part,supported by the Centre of Allergy and Mucosal Immunity,Headquarters of University Advancement at the National Cheng Kung University,Ministry of Education,Taiwan.H.J.T is supported in part by a grant from the National Health Research Institutes(PI:Tsai,PH-101-PP-14,PH-101-SP-14,and PH-108-PP-08).
文摘Virus-induced asthma is prevalent among children,but its underlying mechanisms are unclear.Accumulated evidence indicates that early-life respiratory virus infection increases susceptibility to allergic asthma.Nonetheless,the relationship between systemic virus infections,such as enterovirus infection,and the ensuing effects on allergic asthma development is unknown.Early-life enterovirus infection was correlated with higher risks of allergic diseases in children.Adult mice exhibited exacerbated mite allergen-induced airway inflammation following recovery from EV-A71 infection in the neonatal period.Bone marrow-derived macrophages(BMDMs)from recovered EV-A71-infected mice showed sustained innate immune memory(trained immunity)that could drive naïve T helper cells toward Th2 and Th17 cell differentiation when in contact with mites.Adoptive transfer of EV-A71-trained BMDMs induced augmented allergic inflammation in naïve recipient mice,which was inhibited by 2-deoxy-D-glucose(2-DG)pretreatment,suggesting that trained macrophages following enterovirus infection are crucial in the progression of allergic asthma later in life.
