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

Jaimar Rincon, Ninoska T. Viera, Maritza Josefina Romero Lucas, Jesus A. Mosquera

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 μg/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.

Original languageEnglish (US)
Pages (from-to)1072-1078
Number of pages7
JournalNephrology Dialysis Transplantation
Volume18
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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Mesangial Cells
Streptococcus
Chemokines
Chemokine CCL2
Chemokine CXCL2
Intercellular Adhesion Molecule-1
Enzyme-Linked Immunosorbent Assay
Glomerulonephritis
rat ICAM1 protein
erythrogenic toxin
Indirect Fluorescent Antibody Technique
Thymidine
Fluorescent Antibody Technique
Culture Media
Leukocytes
Cell Culture Techniques
Biopsy
Therapeutics
Serum

Keywords

  • Erythrogenic toxin
  • Glomerulonephritis
  • Intercellular adhesion molecule-1
  • Macrophage inflammatory protein-2
  • Monocyte chemottractant protein-1
  • Proliferation

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

@article{09620b709a6248c8a22c1b5ce07120ca,
title = "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",
abstract = "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 μg/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.",
keywords = "Erythrogenic toxin, Glomerulonephritis, Intercellular adhesion molecule-1, Macrophage inflammatory protein-2, Monocyte chemottractant protein-1, Proliferation",
author = "Jaimar Rincon and Viera, {Ninoska T.} and {Romero Lucas}, {Maritza Josefina} and Mosquera, {Jesus A.}",
year = "2003",
month = "6",
day = "1",
doi = "10.1093/ndt/gfg109",
language = "English (US)",
volume = "18",
pages = "1072--1078",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - 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

AU - Rincon, Jaimar

AU - Viera, Ninoska T.

AU - Romero Lucas, Maritza Josefina

AU - Mosquera, Jesus A.

PY - 2003/6/1

Y1 - 2003/6/1

N2 - 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 μg/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.

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 μg/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.

KW - Erythrogenic toxin

KW - Glomerulonephritis

KW - Intercellular adhesion molecule-1

KW - Macrophage inflammatory protein-2

KW - Monocyte chemottractant protein-1

KW - Proliferation

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U2 - 10.1093/ndt/gfg109

DO - 10.1093/ndt/gfg109

M3 - Article

VL - 18

SP - 1072

EP - 1078

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 6

ER -