Modulation of fibroblast functions by interleukin 1: Increased steady-state accumulation of type I procollagen messenger RNAs and stimulation of other functions but not chemotaxis by human recombinant interleukin 1α and β

Arnold Postlethwaite, Rajendra Raghow, G. P. Stricklin, H. Poppleton, J. M. Seyer, Andrew Kang

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

Interleukin-1 (IL-1) is synthesized by and released from macrophages in response to a variety of stimuli and appears to play an essential role in virtually all inflammatory conditions. In tissues of mesenchymal origin (e.g., cartilage, muscle, bone, and soft connective tissue) IL-1 induced changes characteristic of both destructive as well as reparative phenomena. Previous studies with natural IL-1 of varying degrees of purity have suggested that it is capable of modulating a number of biological activities of fibroblasts. We have compared the effects of purified human recombinant (hr) IL-1α and β on several fibroblast functions. The parameters studied include cell proliferation, chemotaxis, and production of collagen, collagenase, tissue inhibitor of metalloproteinase (TIMP), and prostaglandin (PG) E2. We observed that hrIL-1s stimulate the synthesis and accumulation of type I procollagen chains. Intracellular degradation of collagen is not altered by the hrIL-1s. Both IL-1s were observed to increase the steady-state levels of pro α1(I) and pro α2(I) mRNAs, indicating that they exert control of type I procollagen gene expression at the pretranslational level. We found that both hrIL-1α and β stimulate synthesis of TIMP, collagenase, PGE2 and growth of fibroblasts in vitro but are not chemotactic for fibroblasts. Although hrIL-1α and β both are able to stimulate production of PGE2 by fibroblasts, inhibition of prostaglandin synthesis by indomethacin has no measurable effect on the ability of the IL-1s to stimulate cell growth or production of collagen and collagenase. Each of the IL-1s stimulated proliferation and collagen production by fibroblasts to a similar degree, however hrIL-1β was found to be less potent than hrIL-1α in stimulating PGE2 production. These observations support the notion that IL-1α and β may both modulate the degradation of collagen at sites of tissue injury by virtue of their ability to stimulate collagenase and PGE2 production by fibroblasts. Furthermore, IL-1α and β might also direct reparative functions of fibroblasts by stimulating their proliferation and synthesis of collagen and TIMP.

Original languageEnglish (US)
Pages (from-to)311-318
Number of pages8
JournalJournal of Cell Biology
Volume106
Issue number2
DOIs
StatePublished - Jan 1 1988

Fingerprint

Chemotaxis
Collagen Type I
Interleukin-1
Fibroblasts
Messenger RNA
Dinoprostone
Collagen
Tissue Inhibitor of Metalloproteinases
Collagenases
Aptitude
Matrix Metalloproteinase Inhibitors
Growth
Indomethacin
Connective Tissue
Prostaglandins
Cartilage
Macrophages
Cell Proliferation
Gene Expression
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

@article{386464d295ff49b0a581de0605c2b59f,
title = "Modulation of fibroblast functions by interleukin 1: Increased steady-state accumulation of type I procollagen messenger RNAs and stimulation of other functions but not chemotaxis by human recombinant interleukin 1α and β",
abstract = "Interleukin-1 (IL-1) is synthesized by and released from macrophages in response to a variety of stimuli and appears to play an essential role in virtually all inflammatory conditions. In tissues of mesenchymal origin (e.g., cartilage, muscle, bone, and soft connective tissue) IL-1 induced changes characteristic of both destructive as well as reparative phenomena. Previous studies with natural IL-1 of varying degrees of purity have suggested that it is capable of modulating a number of biological activities of fibroblasts. We have compared the effects of purified human recombinant (hr) IL-1α and β on several fibroblast functions. The parameters studied include cell proliferation, chemotaxis, and production of collagen, collagenase, tissue inhibitor of metalloproteinase (TIMP), and prostaglandin (PG) E2. We observed that hrIL-1s stimulate the synthesis and accumulation of type I procollagen chains. Intracellular degradation of collagen is not altered by the hrIL-1s. Both IL-1s were observed to increase the steady-state levels of pro α1(I) and pro α2(I) mRNAs, indicating that they exert control of type I procollagen gene expression at the pretranslational level. We found that both hrIL-1α and β stimulate synthesis of TIMP, collagenase, PGE2 and growth of fibroblasts in vitro but are not chemotactic for fibroblasts. Although hrIL-1α and β both are able to stimulate production of PGE2 by fibroblasts, inhibition of prostaglandin synthesis by indomethacin has no measurable effect on the ability of the IL-1s to stimulate cell growth or production of collagen and collagenase. Each of the IL-1s stimulated proliferation and collagen production by fibroblasts to a similar degree, however hrIL-1β was found to be less potent than hrIL-1α in stimulating PGE2 production. These observations support the notion that IL-1α and β may both modulate the degradation of collagen at sites of tissue injury by virtue of their ability to stimulate collagenase and PGE2 production by fibroblasts. Furthermore, IL-1α and β might also direct reparative functions of fibroblasts by stimulating their proliferation and synthesis of collagen and TIMP.",
author = "Arnold Postlethwaite and Rajendra Raghow and Stricklin, {G. P.} and H. Poppleton and Seyer, {J. M.} and Andrew Kang",
year = "1988",
month = "1",
day = "1",
doi = "10.1083/jcb.106.2.311",
language = "English (US)",
volume = "106",
pages = "311--318",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "2",

}

TY - JOUR

T1 - Modulation of fibroblast functions by interleukin 1

T2 - Increased steady-state accumulation of type I procollagen messenger RNAs and stimulation of other functions but not chemotaxis by human recombinant interleukin 1α and β

AU - Postlethwaite, Arnold

AU - Raghow, Rajendra

AU - Stricklin, G. P.

AU - Poppleton, H.

AU - Seyer, J. M.

AU - Kang, Andrew

PY - 1988/1/1

Y1 - 1988/1/1

N2 - Interleukin-1 (IL-1) is synthesized by and released from macrophages in response to a variety of stimuli and appears to play an essential role in virtually all inflammatory conditions. In tissues of mesenchymal origin (e.g., cartilage, muscle, bone, and soft connective tissue) IL-1 induced changes characteristic of both destructive as well as reparative phenomena. Previous studies with natural IL-1 of varying degrees of purity have suggested that it is capable of modulating a number of biological activities of fibroblasts. We have compared the effects of purified human recombinant (hr) IL-1α and β on several fibroblast functions. The parameters studied include cell proliferation, chemotaxis, and production of collagen, collagenase, tissue inhibitor of metalloproteinase (TIMP), and prostaglandin (PG) E2. We observed that hrIL-1s stimulate the synthesis and accumulation of type I procollagen chains. Intracellular degradation of collagen is not altered by the hrIL-1s. Both IL-1s were observed to increase the steady-state levels of pro α1(I) and pro α2(I) mRNAs, indicating that they exert control of type I procollagen gene expression at the pretranslational level. We found that both hrIL-1α and β stimulate synthesis of TIMP, collagenase, PGE2 and growth of fibroblasts in vitro but are not chemotactic for fibroblasts. Although hrIL-1α and β both are able to stimulate production of PGE2 by fibroblasts, inhibition of prostaglandin synthesis by indomethacin has no measurable effect on the ability of the IL-1s to stimulate cell growth or production of collagen and collagenase. Each of the IL-1s stimulated proliferation and collagen production by fibroblasts to a similar degree, however hrIL-1β was found to be less potent than hrIL-1α in stimulating PGE2 production. These observations support the notion that IL-1α and β may both modulate the degradation of collagen at sites of tissue injury by virtue of their ability to stimulate collagenase and PGE2 production by fibroblasts. Furthermore, IL-1α and β might also direct reparative functions of fibroblasts by stimulating their proliferation and synthesis of collagen and TIMP.

AB - Interleukin-1 (IL-1) is synthesized by and released from macrophages in response to a variety of stimuli and appears to play an essential role in virtually all inflammatory conditions. In tissues of mesenchymal origin (e.g., cartilage, muscle, bone, and soft connective tissue) IL-1 induced changes characteristic of both destructive as well as reparative phenomena. Previous studies with natural IL-1 of varying degrees of purity have suggested that it is capable of modulating a number of biological activities of fibroblasts. We have compared the effects of purified human recombinant (hr) IL-1α and β on several fibroblast functions. The parameters studied include cell proliferation, chemotaxis, and production of collagen, collagenase, tissue inhibitor of metalloproteinase (TIMP), and prostaglandin (PG) E2. We observed that hrIL-1s stimulate the synthesis and accumulation of type I procollagen chains. Intracellular degradation of collagen is not altered by the hrIL-1s. Both IL-1s were observed to increase the steady-state levels of pro α1(I) and pro α2(I) mRNAs, indicating that they exert control of type I procollagen gene expression at the pretranslational level. We found that both hrIL-1α and β stimulate synthesis of TIMP, collagenase, PGE2 and growth of fibroblasts in vitro but are not chemotactic for fibroblasts. Although hrIL-1α and β both are able to stimulate production of PGE2 by fibroblasts, inhibition of prostaglandin synthesis by indomethacin has no measurable effect on the ability of the IL-1s to stimulate cell growth or production of collagen and collagenase. Each of the IL-1s stimulated proliferation and collagen production by fibroblasts to a similar degree, however hrIL-1β was found to be less potent than hrIL-1α in stimulating PGE2 production. These observations support the notion that IL-1α and β may both modulate the degradation of collagen at sites of tissue injury by virtue of their ability to stimulate collagenase and PGE2 production by fibroblasts. Furthermore, IL-1α and β might also direct reparative functions of fibroblasts by stimulating their proliferation and synthesis of collagen and TIMP.

UR - http://www.scopus.com/inward/record.url?scp=0023901511&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023901511&partnerID=8YFLogxK

U2 - 10.1083/jcb.106.2.311

DO - 10.1083/jcb.106.2.311

M3 - Article

C2 - 2828381

AN - SCOPUS:0023901511

VL - 106

SP - 311

EP - 318

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 2

ER -