scholarly journals AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity

2016 ◽  
Vol 113 (32) ◽  
pp. E4671-E4680 ◽  
Author(s):  
Antonia Di Micco ◽  
Gianluca Frera ◽  
Jérôme Lugrin ◽  
Yvan Jamilloux ◽  
Erh-Ting Hsu ◽  
...  

Inflammasomes are critical sensors that convey cellular stress and pathogen presence to the immune system by activating inflammatory caspases and cytokines such as IL-1β. The nature of endogenous stress signals that activate inflammasomes remains unclear. Here we show that an inhibitor of the HIV aspartyl protease, Nelfinavir, triggers inflammasome formation and elicits an IL-1R–dependent inflammation in mice. We found that Nelfinavir impaired the maturation of lamin A, a structural component of the nuclear envelope, thereby promoting the release of DNA in the cytosol. Moreover, deficiency of the cytosolic DNA-sensor AIM2 impaired Nelfinavir-mediated inflammasome activation. These findings identify a pharmacologic activator of inflammasome and demonstrate the role of AIM2 in detecting endogenous DNA release upon perturbation of nuclear envelope integrity.

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Larissa M. N. Pereira ◽  
Patrícia A. Assis ◽  
Natalia M. de Araújo ◽  
Danielle F. Durso ◽  
Caroline Junqueira ◽  
...  

Abstract Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFα and IL-1β and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human disease.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1725
Author(s):  
Qiuyun Xu ◽  
Xiaorong Zhou ◽  
Warren Strober ◽  
Liming Mao

Inflammasomes are multiprotein complexes formed to regulate the maturation of pro-inflammatory caspases, in response to intracellular or extracellular stimulants. Accumulating studies showed that the inflammasomes are implicated in the pathogenesis of inflammatory bowel disease (IBD), although their activation is not a decisive factor for the development of IBD. Inflammasomes and related cytokines play an important role in the maintenance of gut immune homeostasis, while its overactivation might induce excess immune responses and consequently cause tissue damage in the gut. Emerging studies provide evidence that some genetic abnormalities might induce enhanced NLRP3 inflammasome activation and cause colitis. In these cases, the colonic inflammation can be ameliorated by blocking NLRP3 activation or its downstream cytokine IL-1β. A number of natural products were shown to play a role in preventing colon inflammation in various experimental colitis models. On the other hand, lack of inflammasome function also causes intestinal abnormalities. Thus, an appropriate regulation of inflammasomes might be a promising therapeutic strategy for IBD intervention. This review aims at summarizing the main findings in these studies and provide an outline for further studies that might contribute to our understanding of the role of inflammasomes in the pathogenesis and therapeutic treatment of IBD.


2016 ◽  
Vol 45 (5) ◽  
pp. 187
Author(s):  
Ariyanto Harsono

The immune function is designed to defendthe body in a safe and efficient way againsta variety of dangerous materials includingtoxins and infectious organisms. Mechanical andbiological barriers prevent the penetration ofexogenous material into the body. Only after thesebarriers have been breached and cells have beendirectly attacked does the immune system come intoplay. By a variety of mechanisms, certain immunecells can directly phagocytose and destroy manypathogens. They require the close cooperation ofsomatic cells, which both alert the immune systemthrough alarm signals and later participate in theeffector phase. This first alarm signal can be groupedtogether as “stress signals”, known as the innateimmune response.


2019 ◽  
Vol 11 (2) ◽  
pp. 79-86
Author(s):  
Cindy Ayustin Noya ◽  
Angkit Kinasih ◽  
Venti Agustina ◽  
R.Rr Maria Dyah Kurniasari

Infeksi saluran pernafasan akut atau yang sering disebut ISPA merupakan infeksi pada saluran pernafasan baik saluran pernafasan atas atau bawah.ISPA juga kebanyakan terjadi pada anak balita karena daya tahan tubuh mereka tidak kuat dalam menghadapi penyakit ISPA. ISPA mengakibatkan kematiansekitar15%-20% per tahun pada usia balita di Negara berkembang. Tujuan penelitian ini adalah untuk mengetahui dan menganalisa peran ibu dalam meningkatkan sistem imun anak dengan ISPA.Metode penelitian yang digunakan dalam penelitian ini adalah kualitatif deskriptif dengan sampel purposive sampling.Populasi dan sampel penelitian ini adalah ibu yang mempunyai anak dengan riwayat dan saat ini menderita penyakit ISPA di Batu Gajah Kota Ambon.Partisipan dalam penelitian ini berjumlah 5 orang. Hasil dari penelitian mendapati 4 kategori yaitu pemberian nutrisi pada anak untuk memenuhi kebutuhan agar sistem imunnya terjaga, kebersihan lingkungan, peran ibu dalam melakukan pencegahan pada anaknya yang mengalami ISPA, dan  peran ibu dalam menjaga dan mempertahankan kesehatan anaknya.   Kata kunci: peran ibu, sistem imun, ispa THE ROLE OF MOTHERS IN INCREASING IMMUNE SYSTEM OF CHILDREN WITH ACUTE RESPIRATORY INFECTION    ABSTRACT Acute respiratory infections or often called ARI is an infection of the upper or lower respiratory tract. ARI occurs mostly in children under the age of five because their endurance is not strong in dealing with ARI. ARI results in deaths of around 15%-20% per year at the age of under-five in developing countries. The purpose of this study was to determine and analyze the role of mothers in improving the immune system of children against ARI. The research method used in this study was qualitative descriptive with a purposive sampling sample. Respondents and samples of this study were five mothers who had children with a history of ARI and currently suffering from the disease in Batu Gajah, Ambon City. The results of the study found 4 categories, namely providing nutrition to children to meet their needs so that their immune systems are maintained, clean environment, mother's role in preventing children with ARI, and mother's role to preserve and maintain the health of their children. The findings indicated that in terms of coping or improving the immune system of a child to avoid ARI, it is necessary to have role the of mothers in providing nutrition so that the immune system is boosted, besides that the mother can prevent and protect her child from various diseases, especially ARI. Keywords: role of mothers, immune system, acute respiratory infections


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 259-261
Author(s):  
Aamir Khan ◽  
Rajni K. Gurmule

Vasavaleha is one of the best medicine given for respiratory diseases. Corona viruses typically affect the respiratory system, causing symptoms such as coughing, fever and shortness of breath. It also affects host immune system of human body. Spreading rate of this disease is very high. Whole world is seeking for the treatment which can uproots this diseases. There in no vaccine available till date against this pandemic disease. Ayurveda mainly focuses on prevention of diseases alongwith its total cure. Rajyakshma Vyadhi is MadhyamMarga Roga as per Ayurveda. It shows many symptoms such as Kasa, Shwasa etc. By overall view of Covid 19, shows its resemblance with Rajyakshma Vyadhi described in Ayurveda. Vasavaleha is a Kalpa which is described in Rogadhikara of Rajyakshma. It shows Kasahara, Shwashara properties. It consists of Vasa, Pipalli, Madhu and Goghrita. These components shows actions like bronchodilation, antitussive effect and many more other actions. Pipalli shows important Rasayana effect. So in present review, we have tried to focus on role of Vasavaleha in the management of Covid 19. This can be used as preventive as well as adjuvant medication in treating Covid 19. There is need of further clinical research to rule of exact action of Vasavaleha against Covid 19.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 716-722
Author(s):  
Sneha Dhakite ◽  
Sadhana Misar Wajpeyi

The “Coronavirus disease 19 (COVID-19)” is caused by “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, a newly discovered member of the Coronaviridae family of viruses which is a highly communicable. There is no effective medical treatment till date for Coronavirus disease hence prevention is the best way to keep disease away. Rasayana proved to be highly efficacious and cost effective for the Prevention and Control of viral infections when vaccines and standard therapies are lacking. Rasayana Chikitsa is one of the eight branches of Ashtanga Ayurveda which helps to maintain healthy life style. Rasayana improves immunity and performs many vital functions of human body. Vyadhikshamatva that is immune mechanism of the body is involved in Prevention of the occurrence of a new disease and it also decreases the virulence and progression of an existing disease. In COVID-19 the Respiratory system mainly get affected which is evident from its symptoms like cold, cough and breathlessness. Here the drugs help in enhancing immune system and strengthening functions of Respiratory system can be useful. For this purpose, the Rasayana like Chyavanprasha, Agastya Haritaki, Pippali Rasayana, Guduchi, Yashtimadhu, Haridra, Ashwagandha, Tulsi are used. Rasayana working on Respiratory system are best for Prevention of Coronavirus and boosting immune system. Rasayana Chikitsa can be effective in the Prevention as well as reducing symptoms of COVID-19.


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