Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis

Iwasaki, Tomoyuki; Kaneko, Naoe; Ito, Yuki; Takeda, Hiroyuki; Sawasaki, Tatsuya; Heike, Toshio; Migita, Kiyoshi; Agematsu, Kazunaga; Kawakami, Atsushi; Morikawa, Shinnosuke; Mokuda, Sho; Kurata, Mie; Masumoto, Junya

doi:10.1155/2016/2597376

Cited by 10 publications

(8 citation statements)

References 22 publications

(19 reference statements)

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“…Mutations in the NOD2 gene are associated with autoinflammatory diseases, Blau syndrome, and early-onset sarcoidosis. 9 Propionibacterium acnes, a possible causative agent of sarcoidosis, was shown to activate NF-kB via NOD1 and NOD2. Two allelic NOD1 polymorphisms, 796G-haplotype and 796A-haplotype, have been identified in Japanese sarcoidosis patients.…”

Section: Nlrs and Tlrsmentioning

confidence: 99%

Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Beijer

Veltkamp

Meek

et al. 2017

Semin Respir Crit Care Med

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Sarcoidosis is a disorder of unknown etiology. It is a systemic disease, frequently involving the lungs, skin, eyes, and lymph nodes. It is characterized by formation of noncaseating granulomas at the site(s) of disease. Sarcoidosis has a complex disease pathogenesis, with involvement of both the innate and adaptive immune systems. Several innate immune system receptors including NOD-like receptors and Toll-like receptors appear to be involved in the development of sarcoidosis as well as cellular players such as dendritic cells and macrophages. Furthermore, lymphocytes from the adaptive immune system including Th1, Th17, regulatory T cells, and B cells are likely to play a role in the sarcoidosis disease pathogenesis as well. Possibly, genetic susceptibility and exposure to particular etiologic agents including mycobacterial and propionibacterial antigens, metals, and silica can cause sarcoidosis. Besides exogenous triggers, also self-compounds such as serum amyloid A and vimentin, have been found to play a role in the development of sarcoidosis. It is likely that sarcoidosis does not have one single cause but rather is the result of the interplay between different etiologic agents and the immune system in predisposed individuals.

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Section: Nlrs and Tlrsmentioning

confidence: 99%

Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Beijer

Veltkamp

Meek

et al. 2017

Semin Respir Crit Care Med

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“…The DNA fragments were cloned into pDONR221 vector using the gateway cloning system (Thermo Fisher Scientific). These expression vectors were generated using LR clonase recombination with pEU-E01-GW-AGIA ( Yano et al, 2016 ) or pEU-E01-GW-bls ( Iwasaki et al, 2016 ) vector for cell-free protein synthesis or transient expression vectors. All primer sequences are listed in Supplementary Table 3 .…”

Section: Methodsmentioning

confidence: 99%

Expression of LhFT1, the Flowering Inducer of Asiatic Hybrid Lily, in the Bulb Scales

et al. 2020

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Asiatic hybrid lily leaves emerge from their bulbs in spring, after cold exposure in winter, and the plant then blooms in early summer. We identified four FLOWERING LOCUS T ( FT )-like genes, LhFT1 , LhFT4 , LhFT6 , and LhFT8 , from an Asiatic hybrid lily. Floral bud differentiation initiated within bulbs before the emergence of leaves. LhFT genes were mainly expressed in bulb scales, and hardly in leaves, in which the FT-like genes of many plants are expressed in response to environmental signals. LhFT1 was expressed in bulb scales after vernalization and was correlated to flower bud initiation in two cultivars with different flowering behaviors. LhFT8 was upregulated in bulb scales after cold exposure and three alternative splicing variants with a nonsense codon were simultaneously expressed. LhFT6 was upregulated in bulb scales after flower initiation, whereas LhFT4 was expressed constantly in all organs. LhFT1 overexpression complemented the late-flowering phenotype of Arabidopsis ft-10 , whereas that of LhFT8 did so partly. LhFT4 and LhFT6 overexpression could not complement. Yeast two-hybrid and in vitro analyses showed that the LhFT1 protein interacted with the LhFD protein. LhFT6 and LhFT8 proteins also interacted with LhFD, as observed in AlphaScreen assay. Based on these results, we revealed that LhFT1 acts as a floral activator during floral bud initiation in Asiatic hybrid lilies. However, the biological functions of LhFT4 , LhFT6 , and LhFT8 remain unclear.

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“…Therefore, the Nod2 nodosome may be an attractive drug target for the treatment of BS/EOS. We aimed to develop a reconstituted protein–protein interaction assay system between wild-type Nod2 and the BS/EOS-associated mutants of Nod2 and RIPK2 in a cell-free system, called the reconstituted Nod2 nodosome in a cell-free system [ 63 ].…”

Section: Reconstituted Nod2 Nodosome In a Cell-free Systemmentioning

confidence: 99%

“…The Nod2 nodosomes with BS/EOS-associated mutations Nod2-R334W and Nod2-N670K were more sensitive to MDP than Nod2-WT. Therefore, we think that our Nod2 nodosome in a cell-free system can be a useful tool for investigating the pathogenesis of BS/EOS and drug discovery [ 63 ].…”

Section: Reconstituted Nod2 Nodosome In a Cell-free Systemmentioning

confidence: 99%

Applications of reconstituted inflammasomes in a cell-free system to drug discovery and elucidation of the pathogenesis of autoinflammatory diseases

et al. 2017

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The inflammasome, typically consisting of a Nod-like receptor, apoptosis-associated speck-like protein, and pro-caspase-1, has recently been identified as a huge intracellular complex, which plays a crucial role in interleukin-1 maturation or specific physiological functions. Two Nod-like receptors, such as nucleotide-binding oligomerization domains-containing protein (Nod)1 and Nod2, interact with the receptor-interacting protein serine-threonine kinase (RIPK)2 accompanied by Iκ-B kinase (IKK) complexes to construct the nodosome, leading to nuclear factor (NF)-κB activation. The aberrant activation of inflammasomes or nodosomes causes autoinflammatory diseases. Therefore, inflammasomes may be attractive targets to treat autoinflammatory diseases. Our aim is to develop reconstituted inflammasomes in a cell-free system to discover specific molecular-target drugs and elucidate the molecular pathogenesis of autoinflammatory diseases. In this review, we describe reconstituted inflammasomes in a cell-free system.

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Nod2-Nodosome in a Cell-Free System: Implications in Pathogenesis and Drug Discovery for Blau Syndrome and Early-Onset Sarcoidosis

Cited by 10 publications

References 22 publications

Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Expression of LhFT1, the Flowering Inducer of Asiatic Hybrid Lily, in the Bulb Scales

Applications of reconstituted inflammasomes in a cell-free system to drug discovery and elucidation of the pathogenesis of autoinflammatory diseases

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