Complementary DNAs coding for two subunits of hamster interleukin-12 (IL-12), p35 and p40, were cloned from a hamster dendritic cell (DC) cDNA library. The cloning demonstrated that hamster IL-12 consisted of a p35 subunit with 216 amino acid (aa) residues and a p40 subunit with 327 aa. Structural comparison of hamster p35 and p40 at the protein level showed the highest homologies with each counterpart of sigmodon (hispid cotton rat). The gene expressions of hamster IL-12 p35 and p40 in bone marrow (BM) cells cultured in the presence of mouse granulocyte macrophage-colony-stimulating factor (mGM-CSF) and IL-4 were up-regulated during culture. Immunoblot analysis of 293 cells transfected with hamster p35 and p40 expression vectors suggested the presence of a covalently linked p35/p40 heterodimer. Furthermore, supernatant from the 293 cells transfected with both expression vectors induced the up-regulation of interferon-gamma (IFN-gamma) mRNA in hamster splenocytes, indicating that the p35/p40 heterodimer IL-12 protein present in the supernatant was functional. These results suggest that the vectors containing hamster IL-12 cDNA might be suitable tools for developing an immunotherapeutic approach against experimental cancer in a hamster model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0161-5890(03)00165-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Association of hyperphosphatemia with renal prognosis in patients with autosomal dominant polycystic kidney disease.
Clin Exp Nephrol
September 2024
Department of Nephrology, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan.
Article Synopsis
- Lower serum phosphate levels in autosomal dominant polycystic kidney disease (ADPKD) may hide the importance of high phosphate levels (hyperphosphatemia) in predicting kidney outcomes.
- A study with 235 ADPKD patients found that increased serum phosphate is a significant risk factor for kidney disease progression, with higher levels correlating with worse outcomes.
- The findings suggest that monitoring phosphate levels, especially when they exceed 3.5 mg/dL, is crucial for managing ADPKD, as they are linked to lower kidney survival rates.
Ebi3 Binding to IFN-γ and IL-10 Limits Their Function.
J Immunol
October 2024
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
EBV-induced gene 3 (Ebi3) is a β subunit within the IL-12 cytokine family that canonically binds to α subunits p19, p28, or p35 to form the heterodimeric cytokines IL-39, IL-27, and IL-35, respectively. In the last decade, the binding partners for Ebi3 have continued to expand to include IL-6 and the other IL-12 family β subunit p40, revealing the possibility that Ebi3 may be able to bind to other cytokines and have distinct functions. We first explored this possibility utilizing an in vivo mouse model of regulatory T cell-restricted deletions of the subunits composing the cytokine IL-35, p35, and Ebi3, and we observed a differential impact on CD8+ T cell inhibitory receptor expression despite comparable reduction in tumor growth.
View Article and Find Full Text PDFImplication of IL-12A, IL-12B, IL-6, and TNF single-nucleotide polymorphisms in severity and susceptibility to COVID-19.
Int J Immunopathol Pharmacol
September 2024
Human Genetics Laboratory, School of Medicine and Pharmacy, University Mohammed V in Rabat, Rabat, Morocco.
Background: The Coronavirus Disease 2019 (COVID-19) pandemic has led to significant global morbidity and mortality. Understanding the genetic factors that influence disease outcomes can provide critical insights into pathogenesis and potential therapeutic targets.
Objective: This study aimed to investigate the potential correlation between single nucleotide polymorphisms (SNPs) in , , , and genes and the severity as well as susceptibility to COVID-19 among Moroccan patients.
The oocyte microenvironment is altered in adolescents compared to oocyte donors.
Hum Reprod Open
August 2024
Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Study Question: Do the molecular signatures of cumulus cells (CCs) and follicular fluid (FF) of adolescents undergoing fertility preservation differ from that of oocyte donors?
Summary Answer: The microenvironment immediately surrounding the oocyte, including the CCs and FF, is altered in adolescents undergoing fertility preservation compared to oocyte donors.
What Is Known Already: Adolescents experience a period of subfecundity following menarche. Recent evidence suggests that this may be at least partially due to increased oocyte aneuploidy.
Structure and assembly of the human IL-12 signaling complex.
Structure
October 2024
The Ministry of Education Key Laboratory of Protein Science, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:
Article Synopsis
- The study investigates the structure of Interleukin (IL)-12, a pro-inflammatory cytokine, using cryoelectron microscopy to understand how it interacts with its receptors IL-12Rβ1 and IL-12Rβ2.
- It reveals that IL-12Rβ2 binds to the IL-12p35 subunit while IL-12Rβ1 attaches to the p40 subunit, highlighting both similarities and differences in receptor interactions compared to other cytokines like IL-23.
- Key residues Y62, Y189, and K192 in IL-12p35 are identified as crucial for receptor binding and signal transduction, providing insights that could lead to new therapeutic strategies targeting IL-12.
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!