Cytokines modulate cilomilast response in lung fibroblasts

Tadashi Kohyama, Xiang-de Liu, Fu Qiang Wen, Tetsu Kobayashi, Qiuhong Fang, Shinji Abe, Lenora Cieslinski, Mary S. Barnette, Stephen I. Rennard

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Fibroblasts, as a major source of extracellular interstitial connective tissue matrix, play an important role in wound healing and the development of fibrosis. The phosphodiesterase (PDE) 4 inhibitor cilomilast inhibits fibroblast chemotaxis and fibroblast-mediated gel contraction. Using the Boyden blindwell chamber chemotaxis assay and the type I collagen gel contraction model, this study investigated whether specific cytokines modulate cilomilast's inhibitory effect through regulation of endogenous PGE2 production. Human recombinant IL-1β stimulated PGE2 production and shifted the cilomilast concentration-dependence curve to the left in both assay systems, indicating increased sensitivity to cilomilast. In contrast, human recombinant IL-4 inhibited PGE2 production and shifted the cilomilast concentration-dependence curve to the right in both systems. In summary, the inhibitory effect of cilomilast on fibroblast migration and collagen gel contraction is modulated by IL-1β and IL-4 through regulation of PGE 2 production.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalClinical Immunology
Volume111
Issue number3
DOIs
StatePublished - Jun 1 2004

Fingerprint

Fibroblasts
Cytokines
Lung
Dinoprostone
Gels
Chemotaxis
Interleukin-1
Interleukin-4
Phosphodiesterase 4 Inhibitors
Collagen Type I
Prostaglandins E
Connective Tissue
Wound Healing
Cilomilast
Fibrosis
Collagen

Keywords

  • Asthma
  • Chronic obstructive lung disease (COPD)
  • Cilomilast
  • Human fetal lung fibroblasts
  • Lung
  • PDE4 inhibitors
  • Prostaglandin E (PGE)
  • Wound healing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kohyama, T., Liu, X., Wen, F. Q., Kobayashi, T., Fang, Q., Abe, S., ... Rennard, S. I. (2004). Cytokines modulate cilomilast response in lung fibroblasts. Clinical Immunology, 111(3), 297-302. https://doi.org/10.1016/j.clim.2004.01.007

Cytokines modulate cilomilast response in lung fibroblasts. / Kohyama, Tadashi; Liu, Xiang-de; Wen, Fu Qiang; Kobayashi, Tetsu; Fang, Qiuhong; Abe, Shinji; Cieslinski, Lenora; Barnette, Mary S.; Rennard, Stephen I.

In: Clinical Immunology, Vol. 111, No. 3, 01.06.2004, p. 297-302.

Research output: Contribution to journalArticle

Kohyama, T, Liu, X, Wen, FQ, Kobayashi, T, Fang, Q, Abe, S, Cieslinski, L, Barnette, MS & Rennard, SI 2004, 'Cytokines modulate cilomilast response in lung fibroblasts', Clinical Immunology, vol. 111, no. 3, pp. 297-302. https://doi.org/10.1016/j.clim.2004.01.007
Kohyama T, Liu X, Wen FQ, Kobayashi T, Fang Q, Abe S et al. Cytokines modulate cilomilast response in lung fibroblasts. Clinical Immunology. 2004 Jun 1;111(3):297-302. https://doi.org/10.1016/j.clim.2004.01.007
Kohyama, Tadashi ; Liu, Xiang-de ; Wen, Fu Qiang ; Kobayashi, Tetsu ; Fang, Qiuhong ; Abe, Shinji ; Cieslinski, Lenora ; Barnette, Mary S. ; Rennard, Stephen I. / Cytokines modulate cilomilast response in lung fibroblasts. In: Clinical Immunology. 2004 ; Vol. 111, No. 3. pp. 297-302.
@article{948c6365d77342dd8580b25eefa80db6,
title = "Cytokines modulate cilomilast response in lung fibroblasts",
abstract = "Fibroblasts, as a major source of extracellular interstitial connective tissue matrix, play an important role in wound healing and the development of fibrosis. The phosphodiesterase (PDE) 4 inhibitor cilomilast inhibits fibroblast chemotaxis and fibroblast-mediated gel contraction. Using the Boyden blindwell chamber chemotaxis assay and the type I collagen gel contraction model, this study investigated whether specific cytokines modulate cilomilast's inhibitory effect through regulation of endogenous PGE2 production. Human recombinant IL-1β stimulated PGE2 production and shifted the cilomilast concentration-dependence curve to the left in both assay systems, indicating increased sensitivity to cilomilast. In contrast, human recombinant IL-4 inhibited PGE2 production and shifted the cilomilast concentration-dependence curve to the right in both systems. In summary, the inhibitory effect of cilomilast on fibroblast migration and collagen gel contraction is modulated by IL-1β and IL-4 through regulation of PGE 2 production.",
keywords = "Asthma, Chronic obstructive lung disease (COPD), Cilomilast, Human fetal lung fibroblasts, Lung, PDE4 inhibitors, Prostaglandin E (PGE), Wound healing",
author = "Tadashi Kohyama and Xiang-de Liu and Wen, {Fu Qiang} and Tetsu Kobayashi and Qiuhong Fang and Shinji Abe and Lenora Cieslinski and Barnette, {Mary S.} and Rennard, {Stephen I.}",
year = "2004",
month = "6",
day = "1",
doi = "10.1016/j.clim.2004.01.007",
language = "English (US)",
volume = "111",
pages = "297--302",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Cytokines modulate cilomilast response in lung fibroblasts

AU - Kohyama, Tadashi

AU - Liu, Xiang-de

AU - Wen, Fu Qiang

AU - Kobayashi, Tetsu

AU - Fang, Qiuhong

AU - Abe, Shinji

AU - Cieslinski, Lenora

AU - Barnette, Mary S.

AU - Rennard, Stephen I.

PY - 2004/6/1

Y1 - 2004/6/1

N2 - Fibroblasts, as a major source of extracellular interstitial connective tissue matrix, play an important role in wound healing and the development of fibrosis. The phosphodiesterase (PDE) 4 inhibitor cilomilast inhibits fibroblast chemotaxis and fibroblast-mediated gel contraction. Using the Boyden blindwell chamber chemotaxis assay and the type I collagen gel contraction model, this study investigated whether specific cytokines modulate cilomilast's inhibitory effect through regulation of endogenous PGE2 production. Human recombinant IL-1β stimulated PGE2 production and shifted the cilomilast concentration-dependence curve to the left in both assay systems, indicating increased sensitivity to cilomilast. In contrast, human recombinant IL-4 inhibited PGE2 production and shifted the cilomilast concentration-dependence curve to the right in both systems. In summary, the inhibitory effect of cilomilast on fibroblast migration and collagen gel contraction is modulated by IL-1β and IL-4 through regulation of PGE 2 production.

AB - Fibroblasts, as a major source of extracellular interstitial connective tissue matrix, play an important role in wound healing and the development of fibrosis. The phosphodiesterase (PDE) 4 inhibitor cilomilast inhibits fibroblast chemotaxis and fibroblast-mediated gel contraction. Using the Boyden blindwell chamber chemotaxis assay and the type I collagen gel contraction model, this study investigated whether specific cytokines modulate cilomilast's inhibitory effect through regulation of endogenous PGE2 production. Human recombinant IL-1β stimulated PGE2 production and shifted the cilomilast concentration-dependence curve to the left in both assay systems, indicating increased sensitivity to cilomilast. In contrast, human recombinant IL-4 inhibited PGE2 production and shifted the cilomilast concentration-dependence curve to the right in both systems. In summary, the inhibitory effect of cilomilast on fibroblast migration and collagen gel contraction is modulated by IL-1β and IL-4 through regulation of PGE 2 production.

KW - Asthma

KW - Chronic obstructive lung disease (COPD)

KW - Cilomilast

KW - Human fetal lung fibroblasts

KW - Lung

KW - PDE4 inhibitors

KW - Prostaglandin E (PGE)

KW - Wound healing

UR - http://www.scopus.com/inward/record.url?scp=2942562534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942562534&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2004.01.007

DO - 10.1016/j.clim.2004.01.007

M3 - Article

C2 - 15183150

AN - SCOPUS:2942562534

VL - 111

SP - 297

EP - 302

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 3

ER -