The NOD-,LRR-,and pyrin domain-containing protein 3(NLRP3)inflammasome is a multiprotein complex involved in the release of mature interleukin-1βand triggering of pyroptosis,which is of paramount importance in a vari...The NOD-,LRR-,and pyrin domain-containing protein 3(NLRP3)inflammasome is a multiprotein complex involved in the release of mature interleukin-1βand triggering of pyroptosis,which is of paramount importance in a variety of physiological and pathological conditions.Over the past decade,considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing(Signal 1)and assembly(Signal 2)involved in NLRP3 inflammasome activation.Recently,a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels.In this review,we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions,posttranslational modifications,and spatiotemporal regulation of the NLRP3 inflammasome machinery.We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly.A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.展开更多
Interstitial lung disease （ILD） is a comprehensive term referring to a group of lung diseases affecting the interstitium of the lung. Idiopathic pulmonary fibrosis （IPF） is the most common idiopathic ILD, and nons...Interstitial lung disease （ILD） is a comprehensive term referring to a group of lung diseases affecting the interstitium of the lung. Idiopathic pulmonary fibrosis （IPF） is the most common idiopathic ILD, and nonspecific interstitial pneumonia （NSIP） is the second most common. As the name suggests, NSIP is diagnosed atter many other diseases are excluded. The main pathological finding in NSIP is homogeneous interstitial inflammation with or without fibrosis. NSIP can be categorized by cellular type or fibrotic type, according to the grade of inflammation and fibrosis. The cellular type has mostly inflammatory lesions with good responses to steroid, but the fibrotic type has a large proportion of fibrosis mixed with inflammatory lesions and a relatively poor response to steroid treatment So far, the exact mechanism underlying idiopathic lED has not been clarified. Determining key regulators of these ILDs will be helpful in the diagnosis and development of novel drugs for ILD.展开更多
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2017R1A5A2015385)by the framework of an international cooperation program managed by the National Research Foundation of Korea(2015K2A2A6002008).
文摘The NOD-,LRR-,and pyrin domain-containing protein 3(NLRP3)inflammasome is a multiprotein complex involved in the release of mature interleukin-1βand triggering of pyroptosis,which is of paramount importance in a variety of physiological and pathological conditions.Over the past decade,considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing(Signal 1)and assembly(Signal 2)involved in NLRP3 inflammasome activation.Recently,a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels.In this review,we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions,posttranslational modifications,and spatiotemporal regulation of the NLRP3 inflammasome machinery.We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly.A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.
文摘Interstitial lung disease （ILD） is a comprehensive term referring to a group of lung diseases affecting the interstitium of the lung. Idiopathic pulmonary fibrosis （IPF） is the most common idiopathic ILD, and nonspecific interstitial pneumonia （NSIP） is the second most common. As the name suggests, NSIP is diagnosed atter many other diseases are excluded. The main pathological finding in NSIP is homogeneous interstitial inflammation with or without fibrosis. NSIP can be categorized by cellular type or fibrotic type, according to the grade of inflammation and fibrosis. The cellular type has mostly inflammatory lesions with good responses to steroid, but the fibrotic type has a large proportion of fibrosis mixed with inflammatory lesions and a relatively poor response to steroid treatment So far, the exact mechanism underlying idiopathic lED has not been clarified. Determining key regulators of these ILDs will be helpful in the diagnosis and development of novel drugs for ILD.
