title: Transforming growth factor-beta suppresses macrophage-induced mesangial cell fibronectin expression.
abstract: BACKGROUND
  We have previously shown that macrophages are able to promote prosclerotic responses in rat mesangial cells. Th2-type cytokines, including interleukin-10 (IL-10), IL-13, and IL-4 as well as transforming growth factor-beta (TGF-beta), are known to have suppressive effects on various aspects of macrophage function. In the current study, we investigated the effect of TGF-beta pretreatment on the ability of macrophages to induce fibronectin expression.
  
  
  RESULTS
  Conditioned medium from TGF-beta pretreated macrophages (MPCM(TGF)) induced lower fibronectin levels in mesangial cells in both the secreted and cell-associated forms, compared with conditioned medium from standard macrophages (MPCM) (5.5 +/- 0.2 vs. 3.4 +/- 0.3 and 4.05 +/- 0.45 vs. 2.3 +/- 0.2-fold increase over medium alone for MPCM versus MPCM(TGF) in supernatants and cell lysates, respectively). Northern blot analysis demonstrated that fibronectin message was marginally reduced to 0.88 +/- 0.04 (P < 0.03 vs. MPCM, N = 3) of MPCM-induced levels. However, mesangial cell transin mRNA levels induced in response to MPCM(TGF) were 2.29 +/- 0.47-fold greater than those induced by standard MPCM (P = 0.03 vs. MPCM, N = 4). TIMP-1 mRNA levels were also increased in response to MPCM(TGF), but only by 1.43 +/- 0.1-fold (P = 0.02 vs. MPCM, N = 5). Casein-FITC digestion studies confirmed that MPCM(TGF) stimulated more mesangial cell caseinolytic activity than did MPCM. In addition, MPCM-mediated up-regulation of mesangial cell TGF-beta mRNA and protein expression was significantly reduced in response to conditioned medium from macrophages pretreated with TGF-beta.
  
  
  CONCLUSIONS
  This study suggests that TGF-beta is able to regulate negatively the profibrotic effects of macrophages on mesangial cells by both enhancing matrix degradation and reducing synthesis.
authors.affiliation: Department of Nephrology, University of Leicester and Leicester General Hospital, Leicester, England, United Kingdom. izap1@le.ac.uk
authors.forename: I Z
authors.initials: IZ
authors.lastname: Pawluczyk
authors.forename: K P
authors.initials: KP
authors.lastname: Harris
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002364:Caseins / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D002364:Caseins; D017077:Culture Media, Conditioned; D005353:Fibronectins; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D019278:Matrix Metalloproteinase 3