Vitamin D modulates prostaglandin E2 synthesis and degradation in human lung fibroblasts

Xiang-de Liu, Amy Nelson, Xingqi Wang, Maha Farid, Yoko Gunji, Jun Ikari, Shun Iwasawa, Hesham E Basma, Carol Feghali-Bostwick, Stephen I. Rennard

Research output: Contribution to journalArticle

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Abstract

Vitamin D insufficiency has been increasingly recognized in the general population worldwide and has been associated with several lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), and respiratory tract infections. Fibroblasts play a critical role in tissue repair and remodeling, which is a key feature of COPD and asthma. Fibroblasts modulate tissue repair by producing and modifying extracellular matrix components and by releasing mediators that act as autocrine or paracrine modulators of tissue remodeling. The current study was designed to investigate if vitamin D alters fibroblast release of key autocrine/paracrine repair factors. First, we demonstrated that human fetal lung (HFL)-1 cells express the vitaminDreceptor (VDR) and that vitamin D, 25-hydroxyvitamin D [25(OH)D], or 1,25- dihydroxyvitamin D [1,25(OH)2D] induce VDR nuclear translocation and increase VDR-DNA binding activity. We next demonstrated that vitamin D, 25(OH)D, and 1,25(OH)2D significantly reduced prostaglandin (PG)E2 production by human lung fibroblasts (HFL-1) but had no effect on transforming growth factor b1, vascular endothelial growth factor, or fibronectin production. Vitamin D, 25(OH)D, and 1,25(OH)2D significantly inhibited IL-1β -induced microsomal PGE synthase (mPGES)-1 expression; in contrast, all three forms of vitamin D stimulated 15-hydroxy PG dehydrogenase, an enzyme that degrades PGE2. Cyclooxygenase-1 and -2 and the other two PGE 2 synthases (mPGES-2 and cytosolic PGE synthase) were not altered by vitamin D, 25(OH)D, or 1,25(OH)2D. Finally, the effect of PGE 2 inhibition by 25(OH)D was observed in adult lung fibroblasts. These findings suggest that vitamin D can regulate PGE2 synthesis and degradation and by this mechanism can modulate fibroblast-mediated tissue repair function.

Original languageEnglish (US)
Pages (from-to)40-50
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume50
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Fibroblasts
Dinoprostone
Vitamin D
Degradation
Prostaglandins E
Lung
Pulmonary diseases
Repair
Tissue
Chronic Obstructive Pulmonary Disease
Asthma
Cyclooxygenase 1
Transforming Growth Factors
Cyclooxygenase 2
Interleukin-1
Fibronectins
Respiratory Tract Infections
Modulators
Vascular Endothelial Growth Factor A
Lung Diseases

Keywords

  • Fibroblasts
  • PGE
  • Vitamin D

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Vitamin D modulates prostaglandin E2 synthesis and degradation in human lung fibroblasts. / Liu, Xiang-de; Nelson, Amy; Wang, Xingqi; Farid, Maha; Gunji, Yoko; Ikari, Jun; Iwasawa, Shun; Basma, Hesham E; Feghali-Bostwick, Carol; Rennard, Stephen I.

In: American journal of respiratory cell and molecular biology, Vol. 50, No. 1, 01.01.2014, p. 40-50.

Research output: Contribution to journalArticle

Liu, X, Nelson, A, Wang, X, Farid, M, Gunji, Y, Ikari, J, Iwasawa, S, Basma, HE, Feghali-Bostwick, C & Rennard, SI 2014, 'Vitamin D modulates prostaglandin E2 synthesis and degradation in human lung fibroblasts', American journal of respiratory cell and molecular biology, vol. 50, no. 1, pp. 40-50. https://doi.org/10.1165/rcmb.2013-0211OC
Liu, Xiang-de ; Nelson, Amy ; Wang, Xingqi ; Farid, Maha ; Gunji, Yoko ; Ikari, Jun ; Iwasawa, Shun ; Basma, Hesham E ; Feghali-Bostwick, Carol ; Rennard, Stephen I. / Vitamin D modulates prostaglandin E2 synthesis and degradation in human lung fibroblasts. In: American journal of respiratory cell and molecular biology. 2014 ; Vol. 50, No. 1. pp. 40-50.
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