Generation and characterization of antagonistic anti-human interleukin (IL)-18 monoclonal antibodies with high affinity: Two types of monoclonal antibodies against full-length IL-18 and the neoepitope of inflammatory caspase-cleaved active IL-18
| Autor: | Makoto Nakakido, Eiji Obayashi, Kiyoshi Migita, Kazuma Sakamoto, Hiroki Kamino, Takeshi Urano, Kenji Kadomatsu, Hiroaki Kato, Yuko Nariai, Atsushi Kawakami, Kouhei Tsumoto, Tomohiro Koga, Tomoko Sugiura, Gyosuke Sakashita |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.drug_class Antibody Affinity Biophysics Immunofluorescence Monoclonal antibody Biochemistry Interferon-gamma 03 medical and health sciences Cell Line Tumor medicine Humans Molecular Biology Caspase 030102 biochemistry & molecular biology medicine.diagnostic_test biology Chemistry Interleukin-18 Antibodies Monoclonal Interleukin Inflammasome Molecular biology Blot HEK293 Cells 030104 developmental biology Caspases Immunoassay Proteolysis biology.protein Inflammation Mediators Antibody medicine.drug |
| Zdroj: | Archives of Biochemistry and Biophysics. 663:71-82 |
| ISSN: | 0003-9861 |
| DOI: | 10.1016/j.abb.2019.01.001 |
| Popis: | Interleukin‐18 (IL‐18) is a pro-inflammatory cytokine that evokes both innate and acquired immune responses. IL-18 is initially synthesized as an inactive precursor and the cleavage for processing into a mature, active molecule is mediated by pro-inflammatory caspases following the activation of inflammasomes. Two types of monoclonal antibodies were raised: anti-IL-1863−68 antibodies which recognize full-length1−193 and cleaved IL-18; and anti-IL-18 neoepitope antibodies which specifically recognize the new N-terminal 37YFGKLESK44 of IL-18 cleaved by pro-inflammatory caspase-1/4. These mAbs were suitable for Western blotting, capillary Western immunoassay (WES), immunofluorescence, immunoprecipitation, and function-blocking assays. WES analysis of these mAbs allowed visualization of the IL-18 bands and provided a molecular weight corresponding to the pro-inflammatory caspase-1/4 cleaved, active form IL-1837−193, and not to the inactive precursor IL-18, in the serum of patients with adult-onset Still's disease (6/14, 42%) and hemophagocytic activation syndrome (2/6, 33%). These monoclonal antibodies will be very useful in IL-18 and inflammasome biology and for diagnostic and therapeutic strategies for inflammatory diseases. |
| Databáze: | OpenAIRE |
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