Excessive ADAM17 activation occurs in uremic patients and may contribute to their immunocompromised status

Autor: Koichi Tatsuta, Tomohiro Sonou, Toru Mima, Yukiko Yamano, Takashi Shigematsu, Masaki Ohya, Yuri Nakashima, Shigeo Negi, Kazuki Kawakami, Mitsuru Yashiro
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Fibroblast growth factor 23
klotho
urologic and male genital diseases
Mice
0302 clinical medicine
Immunology and Allergy
Medicine
Klotho
Glucuronidase
Original Research
Aged
80 and over
Metalloproteinase
medicine.diagnostic_test
Middle Aged
medicine.anatomical_structure
Female
lcsh:Immunologic diseases. Allergy
medicine.medical_specialty
Immunology
ADAM17 Protein
Peripheral blood mononuclear cell
Cell Line
Flow cytometry
Immunocompromised Host
03 medical and health sciences
Immune system
Renal Dialysis
Immunity
Internal medicine
CKD
Animals
Humans
Renal Insufficiency
Chronic
Klotho Proteins
B cell
Aged
Uremia
TACE
business.industry
Fibroblast Growth Factors
Fibroblast Growth Factor-23
030104 developmental biology
Endocrinology
Case-Control Studies
Leukocytes
Mononuclear
business
lcsh:RC581-607
030215 immunology
Zdroj: Immunity, Inflammation and Disease, Vol 8, Iss 2, Pp 228-235 (2020)
Immunity, Inflammation and Disease
ISSN: 2050-4527
Popis: Introduction We previously reported that fibroblast growth factor 23 (FGF23)‐klotho signaling plays a role in B cell immunity. Despite high serum levels of FGF23, a decline in immunity is frequently observed in patients on hemodialysis (HD); thus, abnormalities in the FGF23‐klotho signaling pathway in immune cells may occur in these patients. Methods We analyzed the number of klotho‐positive cells in peripheral blood mononuclear cells from 10 male and 6 female patients on HD and 5 healthy male subjects using flow cytometry. We analyzed the abundance of cleaved klotho protein in the murine B cell line, A20, and in the serum of HD patients and healthy subjects (HS) using flow cytometry and Western blotting. The serum level of A disintegrin and metalloprotease 17 (ADAM17) was measured in HD patients and HS using enzyme‐linked immunosorbent assay. Results The number of klotho‐positive B cells was reduced in HD patients. Serum ADAM17 was responsible for the reduction in klotho, as a specific ADAM17 inhibitor reversed this change. The total serum levels of ADAM17 were similar in HD patients and HS; however, activated ADAM17 was increased in the serum of HD patients. Conclusions We concluded that abnormal ADAM17 activation could contribute to the immunocompromised status in patients on HD, in line with the reported role of ADAM17 as an anti‐inflammatory and immunosuppressive factor.
Klotho expression of lymphocyte was lower in the uremic patients (hemodialysis patient) than in healthy subjects, which was one of the causes for a decrease in a number of lymphocyte and immunocompromised status in uremic patients. It was one of the causes for the lower expression of klotho in lymphocyte of the patient that activated A disintegrin and metalloprotease 17 cleavaged klotho in lymphocyte.
Databáze: OpenAIRE
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