RRC ID 58818
著者 Yashiro M, Ohya M, Mima T, Nakashima Y, Kawakami K, Sonou T, Tatsuta K, Yamano Y, Negi S, Shigematsu T.
タイトル Excessive ADAM17 activation occurs in uremic patients and may contribute to their immunocompromised status.
ジャーナル Immun Inflamm Dis
Abstract 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.
巻・号 8(2)
ページ 228-235
公開日 2020-6-1
DOI 10.1002/iid3.298
PMID 32180373
PMC PMC7212198
MeSH ADAM17 Protein / blood* ADAM17 Protein / genetics Aged Aged, 80 and over Animals Case-Control Studies Cell Line Female Fibroblast Growth Factor-23 Fibroblast Growth Factors / blood* Fibroblast Growth Factors / genetics Glucuronidase / blood* Glucuronidase / genetics Humans Immunocompromised Host Klotho Proteins Leukocytes, Mononuclear / metabolism* Male Mice Middle Aged Renal Dialysis Renal Insufficiency, Chronic / blood Renal Insufficiency, Chronic / genetics* Renal Insufficiency, Chronic / therapy Uremia / blood Uremia / genetics
IF 2.5
引用数 0
リソース情報
ヒト・動物細胞 A20(RCB2745)