Potential therapeutic antibodies targeting specific adiponectin isoforms in rheumatoid arthritis
| Autor: | Chun Jeih Ryu, Dae-Hyun Hahm, Hyun Min Lee, Kyoung Soo Kim, Hyung-In Yang, Yeon-Ah Lee, Jung Yeon Kim, Bonjun Sur |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene isoform Male Monoclonal antibody lcsh:Diseases of the musculoskeletal system CIA (collagen-induced arthritis) mouse model medicine.drug_class Adiponectin isomer Clone (cell biology) Arthritis law.invention Arthritis Rheumatoid Therapeutic antibody 03 medical and health sciences Mice 0302 clinical medicine Drug Delivery Systems law medicine Human Umbilical Vein Endothelial Cells Animals Humans Protein Isoforms Rheumatoid arthritis Aged 030203 arthritis & rheumatology Mice Inbred BALB C biology Adiponectin Chemistry Antibodies Monoclonal Middle Aged medicine.disease Molecular biology Blot 030104 developmental biology Mice Inbred DBA biology.protein Recombinant DNA Female Antibody lcsh:RC925-935 Hybridoma Research Article |
| Zdroj: | Arthritis Research & Therapy, Vol 20, Iss 1, Pp 1-12 (2018) Arthritis Research & Therapy |
| ISSN: | 1478-6362 |
| Popis: | Background Different adiponectin isoforms appear to be differentially involved in the pathogenesis of various diseases. The purpose of this study was to generate monoclonal antibodies (mAbs) specific to different adiponectin isoforms and investigate whether these mAbs have potential as therapeutic agents for such diseases. Methods Hybridoma cells producing monoclonal antibodies were generated and screened using enzyme-linked immunosorbent assay and Western blotting for the production of mAbs recognizing human adiponectin isoforms. Results The mAb from hybridoma clone KH7–41 recognized both the middle molecular weight (MMW) (hexamer) and low molecular weight (LMW) (trimer) isoforms of adiponectin in human serum, whereas the KH7–33 mAb detected only MMW (hexamer) adiponectin. The KH4–8 clone recognized both the high molecular weight (HMW) (multimer) and MMW adiponectin isoforms. However, in mouse and rat sera, the abovementioned antibodies recognized only the MMW isomer. These mAbs also recognized adiponectin in various human tissues, such as lung, kidney, and adipose tissues, although the three mAbs had different staining intensities. The mAb from clone KH4–8 effectively inhibited increases in interleukin-6 (IL-6) and IL-8 expression in recombinant adiponectin-stimulated human osteoblasts and human umbilical vein endothelial cells. Also, the mAbs KH7–33 and KH4–8 significantly ameliorated rheumatic symptoms in a collagen-induced arthritis mouse model. This result suggests that these mAb treatments may ameliorate adiponectin-mediated inflammatory response. Conclusions mAbs against human adiponectin isomers can potentially be developed as therapeutic antibodies to target specific detrimental isoforms of adiponectin while maintaining the functions of beneficial isoforms. Electronic supplementary material The online version of this article (10.1186/s13075-018-1736-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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