Both the lung and the thymus are vital target organ for pathogens including viruses. The immunoproteasome (i-proteasome) enhances antigen presentation for MHC class I molecules to activate CD8+T lymphocyte. These facilitate antiviral adaptive immune response. Our previous study found that, expression of i-proteasome subunits in porcine lung was altered during normal and inflammatory conditions. To date, the expression of i-proteasome subunits in porcine thymus to viruses has not been investigated. In the present study, LMP2, LMP7, and MECL-1 were cloned, identified and their sequences encoded predicted proteins of 216, 275, and 278 amino acids, respectively. Expression of LMP2, LMP7, and MECL-1, in the cytoplasm and nucleus, was markedly altered in the porcine reproductive and respiratory syndrome virus (PRRSV)-infected lung and thymus. And dendritic cells and epithelial cells readily expressed the i-proteasome subunit LMP2 in the thymus of PRRSV-infected pigs compared to that in mock-infected pigs. Additionally, the in vitro stimulation of a PAM cell line with PolyI:C for 12 and 24 h resulted in increased LMP2, LMP7, and MECL-1 expression. These results suggest a central role for these complexes in the activation of an antiviral immune response in pigs. A better understanding of the role of the i-proteasome in different cell types, tissues, and hosts could improve vaccine design and facilitate the development of effective treatment strategies for viral infections.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2018.05.190DOI Listing

Publication Analysis

Top Keywords

lmp2 lmp7
16
lmp7 mecl-1
16
immune response
12
lung thymus
12
expression i-proteasome
8
i-proteasome subunits
8
subunits porcine
8
thymus
5
expression
5
lmp2
5

Similar Publications

Targeting Immunoproteasome in Polarized Macrophages Ameliorates Experimental Emphysema Via Activating NRF1/2-P62 Axis and Suppressing IRF4 Transcription.

Adv Sci (Weinh)

November 2024

Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, The First Affiliated Hospital (Shenzhen People's Hospital) and School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.

Article Synopsis
  • * Research indicates that inhibiting the immunoproteasome can reduce inflammation and improve lung function in COPD models, particularly through the use of the inhibitor ONX-0914.
  • * ONX-0914 shows improved efficacy when delivered in PLGA nanoparticles, effectively targeting macrophages and modulating their polarization, making it a promising therapeutic approach for COPD.
View Article and Find Full Text PDF

Embryonic stem cells (ESCs) are remarkable for the high activity level of ubiquitin-proteasome system-the molecular machinery of protein degradation in the cell. Various forms of the proteasome complexes comprising different subunits and interacting regulators are responsible for the substrate selectivity and degradation. Immunoproteasomes are amongst these forms which play an important role in antigen presentation; however, a body of recent evidence suggests their functions in pluripotent stem cells.

View Article and Find Full Text PDF

Optimization of α-amido boronic acids via cryo-electron microscopy analysis: Discovery of a novel highly selective immunoproteasome subunit LMP7 (β5i)/LMP2 (β1i) dual inhibitor.

Bioorg Med Chem

July 2024

Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Electronic address:

The immunoproteasome subunit LMP7 (β5i)/LMP2 (β1i) dual blockade has been reported to suppress B cell differentiation and activation, suggesting that the dual inhibition of LMP7/LMP2 is a promising approach for treating autoimmune diseases. In contrast, the inhibition of the constitutive proteasome subunit β5c correlates with cytotoxicity against non-immune cells. Therefore, LMP7/LMP2 dual inhibitors with high selectivity over β5c may be desirable for treating autoimmune diseases.

View Article and Find Full Text PDF

Inhibition of Immunoproteasome Attenuates NLRP3 Inflammasome Response by Regulating E3 Ubiquitin Ligase TRIM31.

Cells

April 2024

Department of Bioscience and Biotechnology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea.

Article Synopsis
  • Excessive pro-inflammatory cytokines disrupt the intestinal barrier in inflammatory bowel disease (IBD), with TNFα playing a significant role by activating the NLRP3 inflammasome and promoting inflammatory responses.
  • Inhibition of the immunoproteasome (IP) using a specific inhibitor (YU102) reduces NLRP3 protein levels and enhances its degradation through the E3 ligase TRIM31, which leads to increased ubiquitination.
  • In a colitis model, treating with YU102 not only lowered NLRP3 levels but also improved colitis symptoms by reducing inflammation in the intestinal epithelium.
View Article and Find Full Text PDF

Immunoproteasomal Inhibition With ONX-0914 Attenuates Atherosclerosis and Reduces White Adipose Tissue Mass and Metabolic Syndrome in Mice.

Arterioscler Thromb Vasc Biol

June 2024

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, the Netherlands (F.H.S., M.A.C.D., J.d.M., J.A., H.D., M.M., M.J.K., P.J.v.S., M.N.A.B.K., G.H.M.v.P., B.S., A.C.F., I.B., J.K.).

Background: Atherosclerosis is the major underlying pathology of cardiovascular disease and is driven by dyslipidemia and inflammation. Inhibition of the immunoproteasome, a proteasome variant that is predominantly expressed by immune cells and plays an important role in antigen presentation, has been shown to have immunosuppressive effects.

Methods: We assessed the effect of ONX-0914, an inhibitor of the immunoproteasomal catalytic subunits LMP7 (proteasome subunit β5i/large multifunctional peptidase 7) and LMP2 (proteasome subunit β1i/large multifunctional peptidase 2), on atherosclerosis and metabolism in LDLr and APOE*3-Leiden.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!