title: Mizoribine selectively attenuates monocyte chemoattractant protein-1 production in cultured human glomerular mesangial cell: a possible benefit of its use in the treatment of lupus nephritis.
abstract: OBJECTIVE
  Mizoribine (MZR) is a selective inhibitor of the inosine monophosphate dehydrogenase - a key enzyme in the de novo pathway of guanine nucleotides - that was developed in Japan. Besides its immunosuppressive effects, MZR has recently been reported to suppress the progression of histologic chronicity via suppression of macrophage infiltration of the interstitium in selected patients with lupus nephritis.
  
  
  METHODS
  We examine the direct effect of MZR in human mesangial cells on the expression of functional molecules including monocyte chemoattractants in cultured human mesangial cells (MCs) treated with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of viral dsRNA, that makes 'pseudoviral' infection, and analyzed the expression of target molecules by reverse transcriptase-polymerase chain reaction and Western blotting. Thereafter, the effect of MZR on the expressions was examined.
  
  
  RESULTS
  Pretreatment of cells with MZR partially, but significantly, attenuates the expression of monocyte chemoattractant protein (MCP)-1 mRNA and protein, whereas the poly IC-induced expressions for the other functional molecules, such as CCL5, fractalkine and IL-8 were not influenced by MZR treatment. On the other hand, pretreatment of cells with tacrolimus did not suppress the expression of MCP-1 mRNA.
  
  
  CONCLUSIONS
  Mizoribine itself selectively attenuated the expression of MCP-1 both mRNA and protein levels in MCs treated with poly IC; that is, a possible model of 'pseudoviral' infection, which may be involved in the pathogenesis of lupus nephritis.
authors.affiliation: Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Aizawa
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tsuruga
authors.forename: Shojiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yuki
authors.initials: Y
authors.lastname: Chiba
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000096:biosynthesis; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology; D050527:Mesangial Cells / Q000187:drug effects* / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D012263:Ribonucleosides; C010052:mizoribine; D003907:Dexamethasone; D007168:IMP Dehydrogenase; D011070:Poly I-C
keywords: human mesangial cells; lupus nephritis; mizoribine; monocyte chemoattractant protein-1; polyinosinic-polycytidylic acid