Interleukin-18: A Novel Participant in the Occurrence, Development, and Drug Therapy of Obliterative Bronchiolitis Postlung Transplantation

Autor: Yanfeng Zhao, Yuping Li, Ping Shu, Xiaoqing Zhang, Wei Zhang, Yanfei Zhang
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Medicine (General)
medicine.medical_specialty
Article Subject
Isograft
Clinical Biochemistry
chemical and pharmacologic phenomena
Azithromycin
030230 surgery
Gastroenterology
Tacrolimus
Organ transplantation
Proinflammatory cytokine
Interferon-gamma
Mice
03 medical and health sciences
R5-920
0302 clinical medicine
Internal medicine
Genetics
Animals
Humans
Transplantation
Homologous
Medicine
RNA
Small Interfering
Bronchiolitis Obliterans
Molecular Biology
Lung
business.industry
Biochemistry (medical)
Interleukin-18
General Medicine
Transplantation
Disease Models
Animal
surgical procedures
operative
Matrix Metalloproteinase 8
Treatment Outcome
030104 developmental biology
medicine.anatomical_structure
Matrix Metalloproteinase 9
Basigin
Interleukin 18
business
Lung Transplantation
Research Article
medicine.drug
Zdroj: Disease Markers
Disease Markers, Vol 2021 (2021)
ISSN: 1875-8630
0278-0240
DOI: 10.1155/2021/5586312
Popis: Background. Obliterative bronchiolitis (OB) was a main cause of deterioration of long-term prognosis in lung transplant recipients after the first posttransplant year. Proinflammatory cytokine interleukin-18 (IL-18) strengthened both the natural immunity and acquired immunity and played an important role in organ transplantation. The roles of IL-18 in the occurrence, development, and drug treatment of OB remained unclear. Methods. Small interfering RNA (siRNA) against mouse IL-18 (siRNA-IL-18) was used to silence IL-18 expression. Mouse heterotopic tracheal transplantation model was used to simulate OB. Recipient mice were divided into 5 groups ( n = 12 ) according to donor mouse strains and drug treatment: isograft group, allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group. The luminal obliteration rates were pathological evaluation. Expressions of cytokines and MMPs were detected by real-time PCR, western blot, and enzyme chain immunosorbent assay (ELISA). Results. The luminal obliteration rates of IL-18 of the siRNA-IL-18 group were significantly lower than those of the negative control group ( p < 0.0001 ) and the blank control group ( p = 0.0002 ). mRNA expressions of IFN-γ, EMMPRIN, MMP-8, and MMP-9 of the siRNA-IL-18 group were significantly lower than those of the negative and blank control groups. No tracheal occlusion occurred in grafts of the isograft group. The rates of tracheal occlusion of the allograft group, allograft+tacrolimus group, allograft+azithromycin group, and allograft+tacrolimus+azithromycin group were 72.17 ± 4.66 %, 40.33 ± 3.00 %, 38.50 ± 2.08 %, and 23.33 ± 3.24 %, respectively. There were significant differences between the 4 groups ( p < 0.001 ). Serum protein expressions of IL-17 ( p = 0.0017 ), IL-18 ( p = 0.0036 ), IFN-γ ( p = 0.0102 ), and MMP-9 ( p = 0.0194 ) were significantly decreased in the allograft+tacrolimus+azithromycin group compared to the allograft group. Conclusions. IL-18 could be a novel molecular involved in the occurrence, development, and drug treatment of OB.
Databáze: OpenAIRE
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