Abstract
This study was undertaken to examine the dynamic response of human peripheral blood mononuclear cells (PBMC) in the secretion of proinflammatory and anti-inflammatory cytokines induced by uromodulin (URO). Levels of tumor necrosis factor-alpha (TNFalpha), TNF soluble receptor (sTNFRI and II), interleukin 1-beta (IL-1beta), and IL-1 receptor antagonist (IL-1Ra) in the supernatants of URO-stimulated PBMC were measured by ELISA. URO stimulated the secretion of all these cytokines in a dose dependent manner except sTNFRI. Peak levels of TNFalpha and IL-1beta were reached at 6-12 h, while 5-10 fold higher in sTNFR II and IL-1Ra levels were observed at 24-48 h after URO stimulation. URO-induced secretion of TNFalpha, IL-1beta, sTNFRII and IL-1Ra could be enhanced by human plasma. Specifically, serum proteins including C3, sCD14 and IgG not only bound to URO but also enhanced URO-induced TNFalpha secretion of PBMC. Collectively, our data suggest that URO might have dual immunomodulating effect through regulating the secretion of proinflammatory and anti-inflammatory cytokines, and that serum binding proteins might enhance this activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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Antigens, CD / biosynthesis
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Carrier Proteins / blood
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Female
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Humans
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1 / biosynthesis
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Interleukin-1 / blood
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Interleukin-1 / metabolism
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Leukocytes, Mononuclear / drug effects*
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Leukocytes, Mononuclear / metabolism*
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Monokines / biosynthesis*
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Monokines / blood
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Monokines / metabolism
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Mucoproteins / blood
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Mucoproteins / pharmacology*
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Pregnancy
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Pregnancy Proteins / pharmacology*
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Receptors, Interleukin-1 / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Sialoglycoproteins / biosynthesis
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Sialoglycoproteins / blood
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Sialoglycoproteins / metabolism
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / metabolism
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Uromodulin
Substances
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Adjuvants, Immunologic
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Antigens, CD
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Carrier Proteins
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IL1RN protein, human
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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Monokines
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Mucoproteins
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Pregnancy Proteins
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Receptors, Interleukin-1
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Receptors, Tumor Necrosis Factor, Type II
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Sialoglycoproteins
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Tumor Necrosis Factor-alpha
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UMOD protein, human
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Uromodulin