Evidence for transforming growth factor-β expression in human leptomeningeal cells and transforming growth factor-β-like activity in human cerebrospinal fluid

Mahlon Johnson, L. I. Gold, H. L. Moses

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

BACKGROUND: Little is known about the factors regulating growth and maintenance of human leptomeningeal cells. The influence of cerebrospinal fluid on these functions is also unknown. Possible mediators include the transforming growth factor-β (TGFβ) family, three closely related peptides that regulate proliferation and numerous other physiologic processes in most mesenchymal cells. EXPERIMENTAL DESIGN: Expression of both mRNA and protein for TGFβ isoforms TGFβ1, TGFβ2, and TGFβ3 as well as TGFβ-competing activity were evaluated in primary human leptomeningeal cultures by Northern blot analysis, immunohistochemistry, and a radioreceptor assay, respectively. TGFβ1, TGFβ2, and TGFβ3 immunoreactivity was also evaluated in brain sections containing leptomeninges from which these cell cultures were established. An additional study analyzed human cerebrospinal fluid for TGFβ-like activity. RESULTS: Transcripts for TGFβ1, TGFβ2 and TGFβ3 were detected in RNA from each of the eight leptomeningeal cultures. Significant TGFβ1 immunoreactivity was detected in leptomeningeal tissue from five of eight cases. TGFβ2 and TGFβ3 immunostaining was seen in eight and seven of the cases, respectively. Similarly, cells cultured from these meninges exhibited variable TGFβ1 and extensive TGFβ2 and TGFβ3 immunoreactivity. Radioreceptor assays of conditioned media from four cultures demonstrated significant latent TGFβ-like activity. TGFβ radioreceptor competing activity was also detected by radioreceptor assay in normal blood-free cerebrospinal fluid from 32 patients without neurological disease. In addition, pooled cerebrospinal fluid (from six additional patients) exhibited dose dependent TGFβ-like activity in the radioreceptor assay, stimulation of AKR-2B cell growth in soft agar and inhibition of growth in CCL-64 cell assays suggesting that cerebrospinal fluid contains TGβ-like activity. CONCLUSIONS: These findings suggest that the human leptomeninges synthesize TGFβ1, TGFβ2 and TGFβ3 and secrete latent TGFβs at least in vitro. Human cerebrospinal fluid may also contain TGFβ isoforms. Collectively, these observations raise the possibility that members of the TGFβ family contribute to biologic processes of the leptomeninges.

Original languageEnglish (US)
Pages (from-to)360-368
Number of pages9
JournalLaboratory Investigation
Volume67
Issue number3
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

Transforming Growth Factors
Human Activities
Cerebrospinal Fluid
Radioligand Assay
Protein Isoforms
Meninges
Conditioned Culture Medium
Growth
Northern Blotting
Agar
Cultured Cells
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
Immunohistochemistry
RNA
Messenger RNA
Peptides
Brain

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

@article{bf393572da604ed8a225044904e3f882,
title = "Evidence for transforming growth factor-β expression in human leptomeningeal cells and transforming growth factor-β-like activity in human cerebrospinal fluid",
abstract = "BACKGROUND: Little is known about the factors regulating growth and maintenance of human leptomeningeal cells. The influence of cerebrospinal fluid on these functions is also unknown. Possible mediators include the transforming growth factor-β (TGFβ) family, three closely related peptides that regulate proliferation and numerous other physiologic processes in most mesenchymal cells. EXPERIMENTAL DESIGN: Expression of both mRNA and protein for TGFβ isoforms TGFβ1, TGFβ2, and TGFβ3 as well as TGFβ-competing activity were evaluated in primary human leptomeningeal cultures by Northern blot analysis, immunohistochemistry, and a radioreceptor assay, respectively. TGFβ1, TGFβ2, and TGFβ3 immunoreactivity was also evaluated in brain sections containing leptomeninges from which these cell cultures were established. An additional study analyzed human cerebrospinal fluid for TGFβ-like activity. RESULTS: Transcripts for TGFβ1, TGFβ2 and TGFβ3 were detected in RNA from each of the eight leptomeningeal cultures. Significant TGFβ1 immunoreactivity was detected in leptomeningeal tissue from five of eight cases. TGFβ2 and TGFβ3 immunostaining was seen in eight and seven of the cases, respectively. Similarly, cells cultured from these meninges exhibited variable TGFβ1 and extensive TGFβ2 and TGFβ3 immunoreactivity. Radioreceptor assays of conditioned media from four cultures demonstrated significant latent TGFβ-like activity. TGFβ radioreceptor competing activity was also detected by radioreceptor assay in normal blood-free cerebrospinal fluid from 32 patients without neurological disease. In addition, pooled cerebrospinal fluid (from six additional patients) exhibited dose dependent TGFβ-like activity in the radioreceptor assay, stimulation of AKR-2B cell growth in soft agar and inhibition of growth in CCL-64 cell assays suggesting that cerebrospinal fluid contains TGβ-like activity. CONCLUSIONS: These findings suggest that the human leptomeninges synthesize TGFβ1, TGFβ2 and TGFβ3 and secrete latent TGFβs at least in vitro. Human cerebrospinal fluid may also contain TGFβ isoforms. Collectively, these observations raise the possibility that members of the TGFβ family contribute to biologic processes of the leptomeninges.",
author = "Mahlon Johnson and Gold, {L. I.} and Moses, {H. L.}",
year = "1992",
month = "1",
day = "1",
language = "English (US)",
volume = "67",
pages = "360--368",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Evidence for transforming growth factor-β expression in human leptomeningeal cells and transforming growth factor-β-like activity in human cerebrospinal fluid

AU - Johnson, Mahlon

AU - Gold, L. I.

AU - Moses, H. L.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - BACKGROUND: Little is known about the factors regulating growth and maintenance of human leptomeningeal cells. The influence of cerebrospinal fluid on these functions is also unknown. Possible mediators include the transforming growth factor-β (TGFβ) family, three closely related peptides that regulate proliferation and numerous other physiologic processes in most mesenchymal cells. EXPERIMENTAL DESIGN: Expression of both mRNA and protein for TGFβ isoforms TGFβ1, TGFβ2, and TGFβ3 as well as TGFβ-competing activity were evaluated in primary human leptomeningeal cultures by Northern blot analysis, immunohistochemistry, and a radioreceptor assay, respectively. TGFβ1, TGFβ2, and TGFβ3 immunoreactivity was also evaluated in brain sections containing leptomeninges from which these cell cultures were established. An additional study analyzed human cerebrospinal fluid for TGFβ-like activity. RESULTS: Transcripts for TGFβ1, TGFβ2 and TGFβ3 were detected in RNA from each of the eight leptomeningeal cultures. Significant TGFβ1 immunoreactivity was detected in leptomeningeal tissue from five of eight cases. TGFβ2 and TGFβ3 immunostaining was seen in eight and seven of the cases, respectively. Similarly, cells cultured from these meninges exhibited variable TGFβ1 and extensive TGFβ2 and TGFβ3 immunoreactivity. Radioreceptor assays of conditioned media from four cultures demonstrated significant latent TGFβ-like activity. TGFβ radioreceptor competing activity was also detected by radioreceptor assay in normal blood-free cerebrospinal fluid from 32 patients without neurological disease. In addition, pooled cerebrospinal fluid (from six additional patients) exhibited dose dependent TGFβ-like activity in the radioreceptor assay, stimulation of AKR-2B cell growth in soft agar and inhibition of growth in CCL-64 cell assays suggesting that cerebrospinal fluid contains TGβ-like activity. CONCLUSIONS: These findings suggest that the human leptomeninges synthesize TGFβ1, TGFβ2 and TGFβ3 and secrete latent TGFβs at least in vitro. Human cerebrospinal fluid may also contain TGFβ isoforms. Collectively, these observations raise the possibility that members of the TGFβ family contribute to biologic processes of the leptomeninges.

AB - BACKGROUND: Little is known about the factors regulating growth and maintenance of human leptomeningeal cells. The influence of cerebrospinal fluid on these functions is also unknown. Possible mediators include the transforming growth factor-β (TGFβ) family, three closely related peptides that regulate proliferation and numerous other physiologic processes in most mesenchymal cells. EXPERIMENTAL DESIGN: Expression of both mRNA and protein for TGFβ isoforms TGFβ1, TGFβ2, and TGFβ3 as well as TGFβ-competing activity were evaluated in primary human leptomeningeal cultures by Northern blot analysis, immunohistochemistry, and a radioreceptor assay, respectively. TGFβ1, TGFβ2, and TGFβ3 immunoreactivity was also evaluated in brain sections containing leptomeninges from which these cell cultures were established. An additional study analyzed human cerebrospinal fluid for TGFβ-like activity. RESULTS: Transcripts for TGFβ1, TGFβ2 and TGFβ3 were detected in RNA from each of the eight leptomeningeal cultures. Significant TGFβ1 immunoreactivity was detected in leptomeningeal tissue from five of eight cases. TGFβ2 and TGFβ3 immunostaining was seen in eight and seven of the cases, respectively. Similarly, cells cultured from these meninges exhibited variable TGFβ1 and extensive TGFβ2 and TGFβ3 immunoreactivity. Radioreceptor assays of conditioned media from four cultures demonstrated significant latent TGFβ-like activity. TGFβ radioreceptor competing activity was also detected by radioreceptor assay in normal blood-free cerebrospinal fluid from 32 patients without neurological disease. In addition, pooled cerebrospinal fluid (from six additional patients) exhibited dose dependent TGFβ-like activity in the radioreceptor assay, stimulation of AKR-2B cell growth in soft agar and inhibition of growth in CCL-64 cell assays suggesting that cerebrospinal fluid contains TGβ-like activity. CONCLUSIONS: These findings suggest that the human leptomeninges synthesize TGFβ1, TGFβ2 and TGFβ3 and secrete latent TGFβs at least in vitro. Human cerebrospinal fluid may also contain TGFβ isoforms. Collectively, these observations raise the possibility that members of the TGFβ family contribute to biologic processes of the leptomeninges.

UR - http://www.scopus.com/inward/record.url?scp=0026649585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026649585&partnerID=8YFLogxK

M3 - Article

C2 - 1328762

AN - SCOPUS:0026649585

VL - 67

SP - 360

EP - 368

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 3

ER -