Immunomodulatory properties of Tamm-Horsfall glycoprotein (THP) and uromodulin.
نویسندگان
چکیده
BACKGROUND Tamm-Horsfall glycoprotein (THP) and uromodulin are the most abundant glycoproteins in non-pregnant women's/men's and pregnant women's urine, respectively. However, the bioactivities of these glycoproteins are still unclear. OBJECTIVE To evaluate the immunomodulatory properties of THP and uromodulin on human peripheral blood mononuclear cells (PBMC) METHODS: THP and uromodulin isolated with diatomaceous earth filtration were subjected to several bioassays, such as MTS viability assay, immunophenotyping and cytokine analysis. RESULTS MTS viability assay and immunophenotyping analysis showed that uromodulin has greater inhibitory activities in suppressing PBMC viability and the percentage of CD4⁺ T helper cells and CD8⁺ cytotoxic T cells, compared to that of THP. In cytokine analysis, THP tended to induce pro-inflammatory cytokines such as IL-1β, TNF and Th1 cytokine IFN-γ; while uromodulin only induced IL-1β and suppressed both Th1 cytokine IFN-γ and Th2 cytokine IL-10. CONCLUSION These results demonstrate that uromodulin has greater immunosuppressive activities and lower inductive property in relation to activation of immune cells, which provides a more tolerant environment for the developing fetus.
منابع مشابه
Evaluation of Glycan Profiles of Tamm-horsfall Glycoprotein and Uromodulin
Uromodulin is well-known to be the more potent immunosuppressive glycoprotein isolated from pregnant women urine, compared to its counterpart, Tamm-Horsfall glycoprotein (THP) isolated from non-pregnant women/male urine. However, structural profiles of these glycoproteins were controversial until today. Hence, this paper aims to identify the pregnancy associated glycosylation changes of THP and...
متن کاملTamm-Horsfall protein or uromodulin: new ideas about an old molecule.
More than 50 years ago, Tamm and Horsfall isolated a mucoprotein from the human urine, and showed that the protein was able to interact and inhibit viral haemagglutination [1,2]. Of interest, the protein was found to be heavily glycosylated, containing up to 30% of its mass in carbohydrates [3]. It was then discovered that the Tamm–Horsfall protein (THP), as it was readily named, was the most a...
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As a consequence of uromodulin gene mutations, individuals develop precocious hyperuricemia, gout, and progressive renal failure. In vitro studies suggest that pathologic accumulation of uromodulin/Tamm-Horsfall glycoprotein (THP) occurs in the endoplasmic reticulum (ER), but the pathophysiology of renal damage is unclear. It was hypothesized that programmed cell death triggered by accumulation...
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Mice lacking a functional cyclooxygenase-2 (COX-2) gene develop abnormal kidneys that contain hypoplastic glomeruli and reduced proximal tubular mass, and they often die of renal failure. A comparison of kidney-specific gene expression between wild-type and COX-2-deficient mice by cDNA microarrays revealed that although more than 500 mRNAs were differentially expressed between the two strains o...
متن کاملDoes Tamm-Horsfall protein-uric acid binding play a significant role in urate homeostasis?
BACKGROUND Mutations in Tamm-Horsfall protein (THP), also known as uromodulin, lead to a group of diseases known as the uromodulin storage disorders. Clinically, these diseases present with tubulo-interstitial damage, progressive renal dysfunction, hyperuricaemia, and gout. However, it remains unclear how a mutation in THP, a protein produced in the thick ascending limb, can cause hyperuricaemi...
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ورودعنوان ژورنال:
- Asian Pacific journal of allergy and immunology
دوره 33 1 شماره
صفحات -
تاریخ انتشار 2015