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1.
Plant Cell Physiol ; 65(8): 1261-1270, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38757819

RESUMO

Xanthomonas species infect many important crops and cause huge yield loss. These pathogens deliver transcription activator-like (TAL) effectors into the cytoplasm of plant cells. TAL effectors move to host nuclei, directly bind to the promoters of host susceptible genes, and activate their transcription. However, the molecular mechanisms by which TAL effectors induce host transcription remain unclear. We herein demonstrated that TAL effectors interacted with the SIMILAR TO RCD ONE (SRO) family proteins OsSRO1a and OsSRO1b in nuclei. A transactivation assay using rice protoplasts indicated that OsSRO1a and OsSRO1b enhanced the activation of the OsSWEET14 promoter by the TAL effector AvrXa7. The AvrXa7-mediated expression of OsSWEET14 was significantly reduced in ossro1a mutants. However, the overexpression of OsSRO1a increased disease resistance by up-regulating the expression of defense-related genes, such as WRKY62 and PBZ1. This was attributed to OsSRO1a and OsSRO1b also enhancing the transcriptional activity of WRKY45, a direct regulator of WRKY62 expression. Therefore, OsSRO1a and OsSRO1b appear to positively contribute to transcription mediated by bacterial TAL effectors and rice transcription factors.


Assuntos
Regulação da Expressão Gênica de Plantas , Oryza , Doenças das Plantas , Proteínas de Plantas , Efetores Semelhantes a Ativadores de Transcrição , Xanthomonas , Oryza/genética , Oryza/microbiologia , Xanthomonas/fisiologia , Xanthomonas/patogenicidade , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Efetores Semelhantes a Ativadores de Transcrição/metabolismo , Efetores Semelhantes a Ativadores de Transcrição/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Resistência à Doença/genética , Regiões Promotoras Genéticas/genética , Interações Hospedeiro-Patógeno/genética
2.
New Phytol ; 236(4): 1441-1454, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36050871

RESUMO

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) initiate immune responses by recognizing pathogen effectors. The rice gene Xa1 encodes an NLR with an N-terminal BED domain, and recognizes transcription activator-like (TAL) effectors of Xanthomonas oryzae pv oryzae (Xoo). Our goal here was to elucidate the molecular mechanisms controlling the induction of immunity by Xa1. We used yeast two-hybrid assays to screen for host factors that interact with Xa1 and identified the AP2/ERF-type transcription factor OsERF101/OsRAP2.6. Molecular complementation assays were used to confirm the interactions among Xa1, OsERF101 and two TAL effectors. We created OsERF101-overexpressing and knockout mutant lines in rice and identified genes differentially regulated in these lines, many of which are predicted to be involved in the regulation of response to stimulus. Xa1 interacts in the nucleus with the TAL effectors and OsERF101 via the BED domain. Unexpectedly, both the overexpression and the knockout lines of OsERF101 displayed Xa1-dependent, enhanced resistance to an incompatible Xoo strain. Different sets of genes were up- or downregulated in the overexpression and knockout lines. Our results indicate that OsERF101 regulates the recognition of TAL effectors by Xa1, and functions as a positive regulator of Xa1-mediated immunity. Furthermore, an additional Xa1-mediated immune pathway is negatively regulated by OsERF101.


Assuntos
Oryza , Xanthomonas , Oryza/metabolismo , Efetores Semelhantes a Ativadores de Transcrição/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resistência à Doença/genética , Leucina/metabolismo , Doenças das Plantas/genética , Regulação da Expressão Gênica de Plantas , Xanthomonas/genética , Nucleotídeos/metabolismo , Percepção , Proteínas de Bactérias/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Arerugi ; 70(2): 127-131, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33692272

RESUMO

A 52-year-old woman presented to a clinic in late August with exacerbated fatigue and dyspnea on exertion for several months. Then, she was referred and admitted to our hospital in late September. Her chest CT showed bilateral diffuse centrilobular micronodules. In her detailed clinical history, she had kept budgerigars indoors for 15 years. These findings suggested she had a bird-related hypersensitivity pneumonitis (BRHP). By a site environmental investigation, 40 budgerigars were kept in a single breeding room and there were large amounts of droppings on the floor. Serum specific antibody for bird antigens and an environmental provocation test were positive. Bronchoalveolar lavage fluid showed lymphocytosis and a low CD4/CD8 ratio. Trans-bronchial lung biopsy showed lymphocytic infiltration of the alveolar wall and interlobular septa. After antigen avoidance as hospitalization, her symptoms and abnormal shadow improved. From these results, the patient was diagnosed as an acute BRHP.BRHP often presents a chronic onset. This case was diagnosed as an acute type despite the 15-years of budgerigars breeding. Increased exposure of antigens due to lack of cleaning after several days' antigen avoidance was suspected with one of the causes of acute onset.


Assuntos
Alveolite Alérgica Extrínseca , Pulmão do Criador de Aves , Alveolite Alérgica Extrínseca/diagnóstico , Antígenos , Pulmão do Criador de Aves/diagnóstico , Dispneia , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
4.
EMBO J ; 35(22): 2468-2483, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27679653

RESUMO

Perception of microbe-associated molecular patterns by host cell surface pattern recognition receptors (PRRs) triggers the intracellular activation of mitogen-activated protein kinase (MAPK) cascades. However, it is not known how PRRs transmit immune signals to MAPK cascades in plants. Here, we identify a complete phospho-signaling transduction pathway from PRR-mediated pathogen recognition to MAPK activation in plants. We found that the receptor-like cytoplasmic kinase PBL27 connects the chitin receptor complex CERK1-LYK5 and a MAPK cascade. PBL27 interacts with both CERK1 and the MAPK kinase kinase MAPKKK5 at the plasma membrane. Knockout mutants of MAPKKK5 compromise chitin-induced MAPK activation and disease resistance to Alternaria brassicicola PBL27 phosphorylates MAPKKK5 in vitro, which is enhanced by phosphorylation of PBL27 by CERK1. The chitin perception induces disassociation between PBL27 and MAPKKK5 in vivo Furthermore, genetic evidence suggests that phosphorylation of MAPKKK5 by PBL27 is essential for chitin-induced MAPK activation in plants. These data indicate that PBL27 is the MAPKKK kinase that provides the missing link between the cell surface chitin receptor and the intracellular MAPK cascade in plants.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/imunologia , Quitina/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Alternaria/imunologia , Alternaria/patogenicidade , Arabidopsis/enzimologia , Arabidopsis/genética , Membrana Celular/metabolismo , Técnicas de Inativação de Genes , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia
5.
J Infect Chemother ; 26(8): 865-869, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32405245

RESUMO

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Surtos de Doenças , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Idoso , COVID-19 , Infecções por Coronavirus/complicações , Complicações do Diabetes/complicações , Feminino , Humanos , Hipertensão/complicações , Japão , Masculino , Pessoa de Meia-Idade , Pandemias , Gravidade do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Prognóstico , SARS-CoV-2 , Navios
6.
Biosci Biotechnol Biochem ; 83(2): 281-290, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30418086

RESUMO

The rice receptor-like cytoplasmic kinase 185 (OsRLCK185) interacts with the chitin receptor complex OsCERK1/CEBiP and positively regulates chitin-induced immune responses including MAP kinase activation, ROS production and defense gene expression. To elucidate the regulatory mechanisms of OsRLCK185-mediated immunity, we searched for interactors of OsRLCK185. OsDRE2a, rice homologs of the yeast Dre2 protein, were identified as novel interactors of OsRLCK185. OsDRE2a interacted with OsRLCK185 at plasma membrane. The conserved cysteine residues in CIAPIN1 domain of OsDRE2a were essential for tight interaction of OsRLCK185. OsDRE2a was phosphorylated by OsRLCK185. The expression of OsDRE2a and OsDRE2b was induced after chitin treatment. Reduction of OsDRE2a and OsDRE2b mRNA levels by RNA interference resulted in the decreased chitin-induced ROS production. Thus, it is likely that OsDRE2 regulates OsRLCK185-mediated immune responses.


Assuntos
Quitina/metabolismo , Oryza/enzimologia , Imunidade Vegetal , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Aminoácidos , Oryza/imunologia , Fosforilação , Proteínas de Plantas/química , Proteínas de Plantas/genética , Ligação Proteica , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Espécies Reativas de Oxigênio/metabolismo , Homologia de Sequência de Aminoácidos
7.
J Shoulder Elbow Surg ; 27(9): 1642-1649, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29941303

RESUMO

BACKGROUND: Although the pronator teres muscle, a major dynamic stabilizer of elbow valgus stress during throwing, frequently presents stiffness, its relationship with elbow injuries in youth baseball players is unknown. This study investigated the relationship between the elasticity of the pronator teres muscle and elbow injuries in youth baseball players. METHODS: The strain ratio (SR) of 15 individuals with osteochondritis dissecans of the humeral capitellum (OCD group), 67 individuals with medial epicondylar fragmentation (medial injury group), and 115 healthy individuals (control group) was measured as the index of the elasticity of the pronator teres muscle using ultrasound strain elastography. In addition, the forearm and glenohumeral joint rotation range of motion was measured. RESULTS: The SR of the throwing arm was significantly higher in the OCD and medial injury groups than in the control group (both P <.001). In the OCD group, the SR was significantly higher in the throwing arm than in the nonthrowing arm (P <.001), whereas in the medial injury group, there was no significant difference between both arms. The glenohumeral joint external rotation range of motion of the throwing arm was moderately negatively correlated with the SR (r = -0.478, P <.001). CONCLUSIONS: Stiffness of the pronator teres muscle was exhibited only in the throwing arm of individuals with OCD and in both arms in individuals with medial elbow injury. These findings may contribute to an accurate evaluation and prevention of elbow injuries in youth baseball players.


Assuntos
Beisebol/lesões , Lesões no Cotovelo , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Osteocondrite Dissecante/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Adolescente , Criança , Elasticidade , Técnicas de Imagem por Elasticidade , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/fisiopatologia , Antebraço , Humanos , Úmero , Masculino , Osteocondrite Dissecante/fisiopatologia , Amplitude de Movimento Articular/fisiologia , Articulação do Ombro/diagnóstico por imagem
8.
Arerugi ; 67(1): 62-66, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29459527

RESUMO

A 47-year old man presented to our hospital with a 6-month history of malaise, cough and dyspnea on exertion. Laboratory testing revealed the severe hyponatremia. A chest X-ray showed bilateral diffuse micronodules. Anti-Trichosporon asahii antibody and environmental provocation test were positive. Bronchoalveolar lavage fluid showed lymphocytosis and low CD4/8 ratio. The specimens obtained by transbronchial lung biopsy revealed alveolitis. Based on these findings, the patient was diagnosed as having summer-type hypersensitivity pneumonitis (SHP). The patient was treated with antigen avoidance and oral corticosteroid. The hyponatremia caused by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was treated with normal saline and water restriction. Serum sodium level was improved with treatment of SHP, which suggested the relevance between SHP and SIADH.


Assuntos
Alveolite Alérgica Extrínseca , Tricosporonose , Anticorpos Antifúngicos , Humanos , Masculino , Pessoa de Meia-Idade , Estações do Ano , Vasopressinas
9.
Plant Cell Physiol ; 58(6): 993-1002, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28371870

RESUMO

Perception of microbe-associated molecular patterns (MAMPs) including chitin by pattern recognition receptors (PRRs) rapidly induces activation of mitogen-activated protein kinase (MAPK) cascades. However, how PRRs transmit immune signals to the MAPK cascade is largely unknown. Recently, Arabidopsis receptor-like cytoplasmic kinase PBL27 has been reported to activate MAPKs through phosphorylation of AtMAPKKK5 in the chitin signaling pathway. In this study, we found that OsRLCK185, a rice ortholog of PBL27, regulates chitin-induced MAPK activation in a similar fashion to PBL27 in rice. Upon chitin perception, OsRLCK185 is phosphorylated by OsCERK1, a component of the chitin receptor complex. OsRLCK185 interacted with OsMAPKKK11 and OsMAPKKK18, rice orthologs of AtMAPKKK5, in yeast two-hybrid assays. Silencing of both OsMAPKKK11 and OsMAPKKK18 significantly reduced chitin-induced activation of OsMPK3 and OsMPK6. Expression levels of OsMAPKKK18 were much higher than that of OsMAPKKK11 in rice cells, which was consistent with the fact that the Osmapkkk11 single mutation did not affect MAPK activation. This result suggested that OsMAPKKK18 plays a more important role than OsMAPKKK11 in the chitin-induced activation of OsMPK3 and OsMPK6. The bimolecular fluorescence complementation (BiFC) experiment indicated that OsRLCK185 interacted with OsMAPKKK18 at the plasma membrane in planta. In vitro phosphorylation experiments showed that OsRLCK185 directly phosphorylates OsMAPKKK18. Furthermore, OsMAPKKK18 interacted with the MAPKK OsMKK4, the upstream component of OsMPK3/6. These results suggested that OsRLCK185 connects the chitin receptor to the MAPK cascade consisting of OsMAPKKK18-OsMKK4-OsMPK3/6. Our data revealed that chitin-induced MAPK activation in rice and Arabidopsis is regulated by common homologous elements.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Quitina/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oryza/enzimologia , Proteínas de Plantas/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Oryza/efeitos dos fármacos , Oryza/metabolismo , Imunidade Vegetal/efeitos dos fármacos , Imunidade Vegetal/genética , Proteínas Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
10.
Arerugi ; 66(10): 1236-1239, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29249757

RESUMO

We report two family members, a 64-year-old woman (patient 1) and her 37-year-old son (patient 2) diagnosed with summer-type hypersensitivity pneumonitis (SHP). Both patients had high serum titers of anti-Trichosporon asahii antibody. The patients lived in the same house and worked in the same barbershop. Patient 1 was diagnosed with SHP in the summer, and she reacted positively to the provocation test at the work place, but not in the house. Patient 2 was diagnosed with SHP in the winter. Generally, SHP develops and is diagnosed in the summer. The home environment is responsible for most cases of familial SHP. Therefore, our cases of familial SHP are unusual and may suggest that the clinical characteristics of SHP have changed, due to alterations in social and environmental conditions.


Assuntos
Hipersensibilidade/imunologia , Pneumonia/imunologia , Trichosporon/imunologia , Tricosporonose/imunologia , Local de Trabalho , Feminino , Humanos , Pessoa de Meia-Idade , Estações do Ano
11.
J Biol Chem ; 289(41): 28569-78, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25128531

RESUMO

Rac/Rop proteins are Rho-type small GTPases that act as molecular switches in plants. Recent studies have identified these proteins as key components in many major plant signaling pathways, such as innate immunity, pollen tube growth, and root hair formation. In rice, the Rac/Rop protein OsRac1 plays an important role in regulating the production of reactive oxygen species (ROS) by the NADPH oxidase OsRbohB during innate immunity. However, the molecular mechanism by which OsRac1 regulates OsRbohB remains unknown. Here, we report the crystal structure of OsRac1 complexed with the non-hydrolyzable GTP analog guanosine 5'-(ß,γ-imido)triphosphate at 1.9 Å resolution; this represents the first active-form structure of a plant small GTPase. To elucidate the ROS production in rice cells, structural information was used to design OsRac1 mutants that displayed reduced binding to OsRbohB. Only mutations in the OsRac1 Switch I region showed attenuated interactions with OsRbohB in vitro. In particular, Tyr(39) and Asp(45) substitutions suppressed ROS production in rice cells, indicating that these residues are critical for interaction with and activation of OsRbohB. Structural comparison of active-form OsRac1 with AtRop9 in its GDP-bound inactive form showed a large conformational difference in the vicinity of these residues. Our results provide new insights into the molecular mechanism of the immune response through OsRac1 and the various cellular responses associated with plant Rac/Rop proteins.


Assuntos
Guanilil Imidodifosfato/química , NADPH Oxidases/química , Oryza/química , Fosfatos de Fosfatidilinositol/química , Proteínas de Plantas/química , Proteínas rac1 de Ligação ao GTP/química , Sequência de Aminoácidos , Arabidopsis/enzimologia , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Escherichia coli/genética , Escherichia coli/metabolismo , Regulação da Expressão Gênica de Plantas , Guanilil Imidodifosfato/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Monoméricas de Ligação ao GTP/química , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Mutação , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Oryza/enzimologia , Oryza/genética , Oryza/imunologia , Oxirredução , Fosfatos de Fosfatidilinositol/metabolismo , Imunidade Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/metabolismo
12.
Plant J ; 79(1): 56-66, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24750441

RESUMO

Recognition of microbe-associated molecular patterns (MAMPs) initiates pattern-triggered immunity in host plants. Pattern recognition receptors (PRRs) and receptor-like cytoplasmic kinases (RLCKs) are the major components required for sensing and transduction of these molecular patterns. However, the regulation of RLCKs by PRRs and their specificity remain obscure. In this study we show that PBL27, an Arabidopsis ortholog of OsRLCK185, is an immediate downstream component of the chitin receptor CERK1 and contributes to the regulation of chitin-induced immunity in Arabidopsis. Knockout of PBL27 resulted in the suppression of several chitin-induced defense responses, including the activation of MPK3/6 and callose deposition as well as in disease resistance against fungal and bacterial infections. On the other hand, the contribution of PBL27 to flg22 signaling appears to be very limited, suggesting that PBL27 selectively regulates defense signaling downstream of specific PRR complexes. In vitro phosphorylation experiments showed that CERK1 preferentially phosphorylated PBL27 in comparison to BIK1, whereas phosphorylation of PBL27 by BAK1 was very low compared with that of BIK1. Thus, the substrate specificity of the signaling receptor-like kinases, CERK1 and BAK1, may determine the preference of downstream RLCKs.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/enzimologia , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/imunologia , Transdução de Sinais , Alternaria/fisiologia , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Quitina/metabolismo , Técnicas de Inativação de Genes , Glucanos/metabolismo , Modelos Biológicos , Fosforilação , Folhas de Planta/enzimologia , Folhas de Planta/genética , Folhas de Planta/imunologia , Folhas de Planta/fisiologia , Plantas Geneticamente Modificadas , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Reconhecimento de Padrão , Especificidade por Substrato , Nicotiana/enzimologia , Nicotiana/genética , Nicotiana/imunologia , Nicotiana/fisiologia
14.
Sci Rep ; 14(1): 165, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168544

RESUMO

An inhibitor of plasminogen activator inhibitor (PAI)-1, TM5614, inhibited thrombosis, inflammation, and fibrosis in several experimental mouse models. To evaluate the efficacy and safety of TM5614 in human COVID-19 pneumonia, phase IIa and IIb trials were conducted. In an open-label, single-arm trial, 26 Japanese COVID-19 patients with mild to moderate pneumonia were treated with 120-180 mg of TM5614 daily, and all were discharged without any notable side effects. Then, a randomized, double-blind, placebo-controlled trial was conducted in Japanese COVID-19 patients with mild to moderate pneumonia. The number of study participants was set to be 50 in each arm. Even after extension of the enrollment period, the number of study participants did not reach the initially intended sample size, and 75 patients were enrolled in the study. The total oxygenation scale from Day 1 to Day 14 as the primary endpoint was 1.5 in the TM5614 group vs 4.0 in the placebo group (p = 0.22), and the number of days of oxygen administration required as the secondary endpoint was 2.0 days in the TM5614 group vs 3.5 days in the placebo group (p = 0.34). Further studies will be necessary to verify the efficacy of PAI-1 inhibition for the treatment of COVID-19 pneumonia.Clinical trial registration: Two studies were conducted: a prospective, multicenter, open-label phase II study at https://jrct.niph.go.jp (jRCT2021200018) (First registration date 18/08/2020) and a prospective, multicenter, randomized, double-blind, placebo-controlled, phase II study at https://jrct.niph.go.jp (jRCT2021210006) (First registration date 28/05/2021).


Assuntos
COVID-19 , Humanos , Animais , Camundongos , SARS-CoV-2 , Inibidor 1 de Ativador de Plasminogênio , Estudos Prospectivos , Pulmão , Método Duplo-Cego , Resultado do Tratamento
15.
Plant J ; 70(3): 389-97, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22142166

RESUMO

Rho family small GTPases are involved in diverse signaling processes including immunity, growth, and development. The activity of Rho GTPases is regulated by cycling between guanosine diphosphate (GDP)-bound inactive and guanosine triphosphate (GTP)-bound active forms, in which guanine nucleotide exchange factors (GEFs) predominantly function to promote activation of the GTPases. In animals, most Rho GEFs possess a Dbl (diffuse B-cell lymphoma) homology (DH) domain which functions as a GEF-catalytic domain. However, no proteins with the DH domain have been identified in plants so far. Instead, plant-specific Rho GEFs with the PRONE domain responsible for GEF activity have been found to constitute a large family in plants. In this study, we found rice homologs of human SWAP70, Oryza sativa (Os) SWAP70A and SWAP70B, containing the DH domain. OsSWAP70A interacted with rice Rho GTPase OsRac1, an important signaling factor for immune responses. The DH domain of OsSWAP70A exhibited the GEF-catalytic activity toward OsRac1 as found in animal Rho GEFs, indicating that plants have the functional DH domains. Transient expression of OsSWAP70A enhanced OsRac1-mediated production of reactive oxygen species in planta. Reduction of OsSWAP70A and OsSWAP70B mRNA levels by RNA interference resulted in the suppression of chitin elicitor-induced defense gene expression and ROS production. Thus, it is likely that OsSWAP70 regulates immune responses through activation of OsRac1.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Oryza/genética , Imunidade Vegetal/genética , Sequência de Aminoácidos , Expressão Gênica/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Dados de Sequência Molecular , Oryza/imunologia , Oryza/metabolismo , Filogenia , Folhas de Planta/genética , Folhas de Planta/imunologia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Interferência de RNA , RNA Mensageiro/genética , RNA de Plantas/genética , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Nicotiana/genética , Nicotiana/metabolismo , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
16.
Biosci Biotechnol Biochem ; 77(4): 796-801, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23563550

RESUMO

Xanthomonas oryzae delivers effector proteins into host cells through a type III secretion system to inhibit host immune responses, but how these effectors suppress host immunity is largely unknown. Here we found that Xoo2875, one of the effectors of X. oryzae, strongly inhibited host resistance to X. oryzae. Transgenic rice plants expressing Xoo2875 exhibited semi-dwarfism and a reduction in Brassinolide-dependent laminar inclination, characteristics of brassinosteroid (BR)-insensitive mutants caused by mutations of the BR receptor. A yeast two-hybrid experiment indicated that Xoo2875 interacted with OsBAK1, an essential component of both microbe-associated molecular patterns (MAMPs) and BR receptors, suggesting that the virulent activity of Xoo2875 is mediated by inhibition of OsBAK1. Expression of Xoo2875 in Arabidopsis cells activated host immune responses, suggesting the presence of intracellular immune receptors that recognize Xoo2875. Because Xoo2875 homologs are highly conserved in Xanthomonas species, the development of Xoo2875-induced immunity is probably a useful strategy to avoid pathogen invasion.


Assuntos
Proteínas de Bactérias/metabolismo , Oryza/imunologia , Oryza/microbiologia , Xanthomonas/metabolismo , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/microbiologia , Proteínas de Bactérias/genética , Brassinosteroides/metabolismo , Espaço Intracelular/imunologia , Espaço Intracelular/microbiologia , Mutação , Oryza/citologia , Oryza/genética , Fenótipo , Plantas Geneticamente Modificadas , Homologia de Sequência de Aminoácidos , Xanthomonas/fisiologia
17.
BMJ Case Rep ; 16(5)2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37130630

RESUMO

A woman in her late 40s presented with multiple abnormal shadows on high-resolution CT (HRCT), was treated with abemaciclib for recurrent right breast cancer post-surgery and chemoradiation therapy. During the 10-month chemotherapy, HRCT revealed a recurrent pattern of a partly appearing and disappearing organising pneumonia pattern without clinical symptoms. Bronchoalveolar lavage analysis revealed lymphocytosis, while transbronchial lung biopsy revealed alveolitis with epithelial cell injury. Based on the diagnosis of drug-induced pneumonitis due to abemaciclib, the discontinuation of abemaciclib and administration of prednisolone were effective. Abnormal shadow on HRCT disappeared gradually, while elevated Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D levels were restored to normal range. This is the first case report of abemaciclib-induced pneumonitis with histology findings. Since the severity of abemaciclib-induced pneumonitis ranges from mild to fatal, regular monitoring of pneumonitis with radiography, HRCT, and measurement of KL-6 and SP-D levels should be considered.


Assuntos
Mucina-1 , Pneumonia , Feminino , Humanos , Mucina-1/metabolismo , Recidiva Local de Neoplasia , Aminopiridinas/efeitos adversos , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico por imagem , Doença Crônica
18.
Plant Cell Physiol ; 53(4): 740-54, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22437844

RESUMO

The Rac/Rop GTPase OsRac1 plays an essential role in rice immunity. However, the regulatory genes acting downstream of OsRac1 are largely unknown. We focused on the RAI1 gene, which is up-regulated in suspension cells expressing a constitutively active form of OsRac1. RAI1 encodes a putative basic helix-loop-helix transcription factor. A microarray analysis of cells transformed with an inducible RAI1 construct showed increased expression of PAL1 and OsWRKY19 genes after induction, suggesting that these genes are regulated by RAI1. This was confirmed using RAI1 T-DNA activation-tagged and RNA interference lines. The PAL1 and OsWRKY19 genes were also up-regulated by sphingolipid and chitin elicitors, and the RAI1 activation-tagged plants had increased resistance to a rice blast fungus. These results indicated that RAI1 is involved in defense responses in rice. RAI1 interacted with OsMAPK3 and OsMAPK6 proteins in vivo and in vitro. Also, RAI1 was phosphorylated by OsMAPK3/6 and OsMKK4-dd in vitro. Overexpression of OsMAPK6 and/or OsMAPK3 together with OsMKK4-dd increased PAL1 and OsWRKY19 expression in rice protoplasts. Therefore, the regulation of PAL1 and OsWRKY19 expression by RAI1 could be controlled via an OsMKK4-OsMAPK3/6 cascade. Co-immunoprecipitation assays indicated that OsMAPK3 and OsRac1 occur in the same complex as OsMAPK6. Taken together, our results indicate that RAI1 could be regulated by OsRac1 through an OsMAPK3/6 cascade. In this study, we have identified RAI1 as the first transcription factor acting downstream of OsRac1. This work will help us to understand the immune system regulated by OsRac1 in rice and its orthologs in other plant species.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Oryza/imunologia , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Imunoprecipitação , Oryza/genética , Imunidade Vegetal/genética , Imunidade Vegetal/fisiologia , Proteínas de Plantas/genética , Ligação Proteica
19.
Nat Commun ; 13(1): 2397, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577789

RESUMO

The U-box type ubiquitin ligase PUB44 positively regulates pattern-triggered immunity in rice. Here, we identify PBI1, a protein that interacts with PUB44. Crystal structure analysis indicates that PBI1 forms a four-helix bundle structure. PBI1 also interacts with WRKY45, a master transcriptional activator of rice immunity, and negatively regulates its activity. PBI1 is degraded upon perception of chitin, and this is suppressed by silencing of PUB44 or expression of XopP, indicating that PBI1 degradation depends on PUB44. These data suggest that PBI1 suppresses WRKY45 activity when cells are in an unelicited state, and during chitin signaling, PUB44-mediated degradation of PBI1 leads to activation of WRKY45. In addition, chitin-induced MAP kinase activation is required for WRKY45 activation and PBI1 degradation. These results demonstrate that chitin-induced activation of WRKY45 is regulated by the cooperation between MAP kinase-mediated phosphorylation and PUB44-mediated PBI1 degradation.


Assuntos
Oryza , Quitina/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oryza/metabolismo , Doenças das Plantas , Imunidade Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
J Biol Chem ; 285(15): 11308-13, 2010 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-20150424

RESUMO

Serotonin is a well known neurotransmitter in mammals and plays an important role in various mental functions in humans. In plants, the serotonin biosynthesis pathway and its function are not well understood. The rice sekiguchi lesion (sl) mutants accumulate tryptamine, a candidate substrate for serotonin biosynthesis. We isolated the SL gene by map-based cloning and found that it encodes CYP71P1 in a cytochrome P450 monooxygenase family. A recombinant SL protein exhibited tryptamine 5-hydroxylase enzyme activity and catalyzed the conversion of tryptamine to serotonin. This pathway is novel and has not been reported in mammals. Expression of SL was induced by the N-acetylchitooligosaccharide (chitin) elicitor and by infection with Magnaporthe grisea, a causal agent for rice blast disease. Exogenously applied serotonin induced defense gene expression and cell death in rice suspension cultures and increased resistance to rice blast infection in plants. We also found that serotonin-induced defense gene expression is mediated by the RacGTPase pathway and by the G alpha subunit of the heterotrimeric G protein. These results suggest that serotonin plays an important role in rice innate immunity.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/fisiologia , Regulação da Expressão Gênica de Plantas , Serotonina/química , Triptaminas/química , Catálise , Parede Celular/metabolismo , Quitina/química , Mapeamento Cromossômico , Clonagem Molecular , Sistema Enzimático do Citocromo P-450/genética , Imunidade Inata , Oryza , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serotonina/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo
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