title: The dynamic responses of pro-inflammatory and anti-inflammatory cytokines of human mononuclear cells induced by uromodulin.
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.
authors.affiliation: Department of Microbiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: S J
authors.initials: SJ
authors.lastname: Su
authors.forename: T M
authors.initials: TM
authors.lastname: Yeh
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D015846:Monokines / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D009088:Mucoproteins / Q000097:blood / Q000494:pharmacology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism; D058949:Uromodulin
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D002352:Carrier Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015846:Monokines; D009088:Mucoproteins; D011257:Pregnancy Proteins; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; C548612:UMOD protein, human; D058949:Uromodulin