Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ORF5-encoded major envelope glycoprotein (GP5) of porcine reproductive and respiratory syndrome virus (PRRSV) is one of the three major structural proteins of this virus. While some porcine convalescent sera and monoclonal antibodies directed against GP4 and GP5 have the capacity to neutralize the virus in vitro, the protein specificity of porcine neutralizing sera has not yet been established. DNA immunization with a plasmid encoding GP5 of PRRSV, under the control of a human cytomegalovirus promoter, induced anti-GP5-specific neutralizing antibodies in pigs and BALB/c mice. The GP5 protein specificity of neutralizing sera was confirmed by immunoblotting and ELISA. Peripheral blood mononuclear cells obtained from DNA-vaccinated pigs underwent blastogenic transformation in the presence of E. coli-expressed recombinant ORF5-encoded protein, indicating the specificity of the cellular immune response to GP5. Following a massive intratracheal challenge with the virulent IAF-Klop strain of PRRSV, DNA-vaccinated pigs were protected from generalized viraemia and the development of typical macroscopic lung lesions that were observed in unvaccinated, virus-challenged controls, as well as in pigs that were immunized with E. coli-expressed GST-ORF5 recombinant fusion protein. Interstitial pneumonitis and broncho-alveolitis were remarkably milder in DNA-vaccinated animals. These results suggest that the GP5 of PRRSV is a good candidate for a subunit recombinant-type vaccine.
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PMID:Immune response in pigs vaccinated with plasmid DNA encoding ORF5 of porcine reproductive and respiratory syndrome virus. 960 13

Tumour necrosis factor (TNF) blockade has become an important immunomodulatory therapy, particularly in patients refractory to conventional immunosuppression, but responses can be unpredictable. Understanding the complex biology of TNF processing may be key to predicting such responses and reduce unwanted side effects. TNF bioavailability is regulated partly by TNF-alpha converting enzyme (TACE) cleavage; however, it can also be cleaved by proteinase-3 (PR-3). We have demonstrated this mechanism previously in healthy human alveolar macrophages (AM), leading us to hypothesize that PR-3-mediated TNF processing may be an important mechanism in inflammatory lung disease. Furthermore, this may be more apparent in diseases with a neutrophil component typical of usual interstitial pneumonia (UIP), compared with sarcoidosis, where lymphocytes predominate. We isolated AM from patients with UIP and sarcoidosis and healthy subjects. We found increased TACE expression on AM in sarcoidosis. In contrast, TACE was not increased in UIP; we found increased cleavage of glutathione S-transferase-proTNF) substrate, relative to both sarcoidosis and healthy controls. Furthermore, cleavage was subject to inhibition by serine protease inhibitor, rather than a TACE inhibitor BB-3103. Cleavage was proportional to the number of neutrophils isolated from bronchoalveolar lavage, whereas there was an inverse relationship between neutrophils and BB-3103 inhibition. There was also increased PR-3 on the AM surface in UIP relative to healthy controls. These data provide evidence for PR-3-mediated cleavage in UIP, which may have implications for future therapeutic targeting of TACE.
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PMID:Tumour necrosis factor-alpha processing in interstitial lung disease: a potential role for exogenous proteinase-3. 1929 64