Fibroblasts Promote Inflammation and Pain via Interleukin-1 α-Induction of the Monocyte Chemoattractant CCL2.

Fibroblasts Promote Inflammation and Pain via Interleukin-1α-Induction of the Monocyte Chemoattractant CCL2.
Am J Pathol. 2017 Dec 14;:
Authors: Paish HL, Kalson NS, Smith GR, Del Carpio Pons A, Baldock TE, Smith N, Swist-Szulik K, Weir DJ, Bardgett M, Deehan DJ, Mann DA, Borthwick LA
Abstract
Fibroblasts persist within fibrotic scar tissue and exhibit considerable phenotypic and functional plasticity. Here, we hypothesized that scar-associated fibroblasts may be a source of stress-induced inflammatory exacerbations and pain. To test this idea we used a human model of surgery-induced fibrosis, total knee arthroplasty (TKA). Using a combination of tissue protein expression profiling and bioinformatics we discovered that many months following TKA the fibrotic joint exists in a state of unresolved chronic inflammation. Moreover, the infrapatellar fat pad, a soft tissue that becomes highly fibrotic in the post-TKA joint, expresses multiple inflammatory mediators including the monocyte chemoattractant CCL2 and the innate immune trigger interleukin-1α (IL-1α). Fibroblasts isolated from the post-TKA fibrotic infrapatellar fat pad express the interleukin-1 receptor and upon exposure to IL-1α polarize to a highly inflammatory state that enables them to stimulate the recruitment of monocytes. Blockade of fibroblast CCL2 or its transcriptional regulator NF-kB prevented IL-1α-induced monocyte recruitment. Clinical investigations discovered ...

Source: The American Journal of Pathology - December 14, 2017 Category: Pathology Authors: Paish HL, Kalson NS, Smith GR, Del Carpio Pons A, Baldock TE, Smith N, Swist-Szulik K, Weir DJ, Bardgett M, Deehan DJ, Mann DA, Borthwick LA Tags: Am J Pathol Source Type: research