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Upregulation of osteopontin expression via the interaction of macrophages and fibroblasts under IL-1b stimulation.

Abstract：

BACKGROUND:Fibrosis is attributed to dysregulation of tissue-remodeling. In remodeling areas, fibroblasts and macrophages actively make contact with each other. Osteopontin (OPN) is a pro-fibrotic molecule, whose expression is upregulated by interleukin (IL)-1β via secretion of its downstream cytokines, such as IL-6. Here, we investigated the effect of interaction between fibroblasts and macrophages under IL-1β stimulation on the expression of OPN. METHODS:We used human lung fibroblasts and THP-1 macrophages differentiated from THP-1 cells using phorbol 12-myristate 13-acetate. These cells were either cultured alone or co-cultured under IL-1β stimulation. Secretion of OPN and IL-6 were examined by enzyme-linked immunosorbent assay, and mRNA expression was assessed by quantitative real-time PCR. The effects of siRNA against IL-6 or OPN on OPN expression were evaluated. RESULTS:OPN expression increased when fibroblasts and THP-1 macrophages were co-cultured under IL-1β stimulation. The siRNA against IL-6 in fibroblasts suppressed the upregulation of OPN expression during co-culture, whereas siRNA against IL-6 in THP-1 macrophages did not. The upregulation of expression of OPN mRNA in fibroblasts or THP-1 macrophages when co-cultured under IL-1β stimulation was mediated by IL-6 from fibroblasts. OPN from THP-1 macrophages was involved in the increase of OPN expression in fibroblasts. CONCLUSIONS:The present study revealed the crosstalk between fibroblasts and THP-1 macrophages under IL-1β stimulation, where IL-6 from fibroblasts, stimulated by IL-1β, upregulated OPN expression in fibroblasts themselves via increase in OPN from THP-1 macrophages. The fibroblasts/macrophages network may induce activation or qualitative changes in both cells, which contributes to inflammation-associated fibrosis.

journal_name

Cytokine

journal_title

Cytokine

authors

Shimodaira T,Matsuda K,Uchibori T,Sugano M,Uehara T,Honda T

doi

10.1016/j.cyto.2018.04.025

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

63-69

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(18)30178-9

journal_volume

110

pub_type

杂志文章

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