PMID- 12748337 OWN - NLM STAT- MEDLINE DCOM- 20031014 LR - 20190513 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 18 IP - 6 DP - 2003 Jun TI - Increased production of chemotactic cytokines and elevated proliferation and expression of intercellular adhesion molecule-1 in rat mesangial cells treated with erythrogenic toxin type B and its precursor isolated from nephritogenic streptococci. PG - 1072-8 AB - BACKGROUND: Previous reports have demonstrated the presence of streptococcal erythrogenic toxin type B (ETB) as well as proliferation and expression of adhesion molecules along with leukocyte infiltrations in biopsies from patients with acute post-streptococcal glomerulonephritis (APSGN). The purpose of the present study was to correlate infiltrative and proliferative events with interactions between ETB or its precursor (ETBP) and intrinsic mesangial cells. METHODS: Rat mesangial cells were cultured with ETB or ETBP (50 micro g/ml) while measuring production of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) and while examining proliferation and expression of intercellular adhesion molecule-1 (ICAM-1). After 24, 48 and 96 h of incubation, MCP-1 and MIP-2 in culture supernatants were assessed by enzyme-linked immunosorbent assay (ELISA). Cells were assessed for proliferation by incorporation of radioactive thymidine and expression of ICAM-1 was measured by indirect immunofluorescence and by cellular ELISA. RESULTS: Compared with controls, treatment with either ETBP or ETB significantly increased MCP-1 and MIP-2 levels in mesangial cell cultures. Mesangial cells also showed elevated proliferation at 96 h of culture when treated with streptococcal proteins. Although production of MCP-1 and MIP-2 was not correlated with proliferation, treatment with ETBP resulted in a significant correlation between MCP-1 production and proliferation. Immunofluorescence studies revealed an increased expression of ICAM-1 in ETBP/ETB-treated mesangial cells. In addition, cellular ELISA studies showed increased absorbance in cultures treated with ETBP/ETB. Finally, low serum concentrations in the culture medium potentiated the stimulatory effect of ETB on MCP-1 production. CONCLUSIONS: Our findings, by demonstrating a role for cationic streptococcal ETB or ETBP in the induction of chemotactic molecules as well as the proliferation and expression of adhesion molecules, delineate an additional possible pathway for the pathogenesis of APSGN. FAU - Rincon, Jaimar AU - Rincon J AD - Instituto de Investigaciones Clinicas Dr. Americo Negrette, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela. FAU - Viera, Ninoska T AU - Viera NT FAU - Romero, Maritza J AU - Romero MJ FAU - Mosquera, Jesus A AU - Mosquera JA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Bacterial Proteins) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL2) RN - 0 (Exotoxins) RN - 0 (Membrane Proteins) RN - 0 (Monokines) RN - 0 (SpeA protein, Streptococcus pyogenes) RN - 0 (erythrogenic toxin) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Animals MH - *Bacterial Proteins MH - Chemokine CCL2/*biosynthesis MH - Chemokine CXCL2 MH - Disease Models, Animal MH - Exotoxins/*pharmacology MH - Glomerulonephritis/immunology/metabolism/microbiology MH - Intercellular Adhesion Molecule-1/*biosynthesis MH - Kidney/cytology/*drug effects/immunology MH - Male MH - *Membrane Proteins MH - Monokines/*biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - *Streptococcus EDAT- 2003/05/16 05:00 MHDA- 2003/10/15 05:00 CRDT- 2003/05/16 05:00 PHST- 2003/05/16 05:00 [pubmed] PHST- 2003/10/15 05:00 [medline] PHST- 2003/05/16 05:00 [entrez] AID - 10.1093/ndt/gfg109 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2003 Jun;18(6):1072-8. doi: 10.1093/ndt/gfg109.