Environmental conditioning in the control of macrophage thrombospondin-1 production

Jezrom B Fordham, Jing Hua, Sarah R Morwood, Lauren P Schewitz-Bowers, Dave A Copland, Andrew D Dick, Lindsay B Nicholson

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)

Abstract

Thrombospondin-1 (TSP-1) is a multifunctional protein which is secreted into the extracellular matrix during inflammation, where it modulates numerous components of the immune infiltrate. Macrophages are a source of TSP-1, which they produce in response to TLR4 mediated signals. Their production of TSP-1 is regulated by environmental signals that establish a threshold for the level of protein secretion that can be induced by LPS stimulation. Th1 and Th2 cytokines raise this threshold which leads to less TSP-1 production, while signals that promote the generation of regulatory macrophages lower it. TSP-1 plays no direct role in the regulation of its own secretion. In vivo in uveitis, in the presence of TLR-4 ligands, TSP-1 is initially produced by recruited macrophages but this decreases in the presence of inflammatory cytokines. The adaptive immune system therefore plays a dominant role in regulating TSP-1 production in the target organ during acute inflammation.
Original languageEnglish
Article number512
Number of pages9
JournalScientific Reports
Volume2
DOIs
Publication statusPublished - 16 Jul 2012

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