IL-33, IL-37, and Vitamin D Interaction Mediate Immunomodulation of Inflammation in Degenerating Cartilage.

Vikrant Rai,Mohamed M Radwan,Devendra K Agrawal

doi:10.3390/antib10040041

Vikrant Rai, Mohamed M Radwan + Show 1 more

Open Access

https://doi.org/10.3390/antib10040041

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Journal: Antibodies	Publication Date: Oct 26, 2021
Citations: 11	License type: CC BY 4.0

Affiliation: Western University of Health Sciences

Abstract

Chronic joint inflammation due to increased secretion of pro-inflammatory cytokines, the accumulation of inflammatory immune cells (mainly macrophages), and vitamin D deficiency leads to cartilage degeneration and the development of osteoarthritis (OA). This study investigated the effect of vitamin D status on the expression of mediators of inflammation including interleukin (IL)-33, IL-37, IL-6, tumor necrosis factor (TNF)-α, toll-like receptors (TLRs), damage-associated molecular patterns (DAMPs), and matrix metalloproteinases (MMPs) in degenerating the cartilage of hyperlipidemic microswine. Additionally, in vitro studies with normal human chondrocytes were conducted to investigate the effect of calcitriol on the expression of IL-33, IL-37, IL-6, TNF-α, TLRs, DAMPs, and MMPs. We also studied the effects of calcitriol on macrophage polarization using THP-1 cells. The results of this study revealed that vitamin D deficiency is associated with an increased expression of IL-33, IL-37, IL-6, TNF-α, TLRs, DAMPs, and MMPs, while vitamin D supplementation is associated with a decreased expression of the former. Additionally, vitamin D deficiency is associated with increased M1, while vitamin D-supplemented microswine cartilage showed increased M2 macrophages. It was also revealed that calcitriol favors M2 macrophage polarization. Taken together, the results of this study suggest that modulating expression of IL-33, IL-6, TNF-α, TLRs, DAMPs, and MMPs with vitamin D supplementation may serve as a novel therapeutic to attenuate inflammation and cartilage degeneration in osteoarthritis.

Highlights

An imbalance between the regenerative and degenerative processes of cartilage with a predominance of degenerative factors results in cartilage damage and the development of osteoarthritis (OA)
We have investigated the effects of vitamin D status on the expression of mediators of inflammation including IL-33, and the effect of calcitriol on the expression levels of IL-33, IL-6, tumor necrosis factor (TNF)-α, toll-like receptors (TLRs), damage-associated molecular patterns (DAMPs), matrix metalloproteinases (MMPs), and macrophage polarization with a hypothesis that vitamin D supplementation attenuates IL-33-mediated inflammation and enhances M2 macrophage polarization, thereby decreasing inflammation in the cartilage
IF showed increased immunopositivity for IL-33 in vitamin D deficient (VDDef) compared to vitamin D sufficient (VDSuff) and vitamin D-supplemented (VDSupp) and in VDSuff compared to VDSupp swine (Figure 1, panels A, E, and I)

Summary

Introduction

An imbalance between the regenerative and degenerative processes of cartilage with a predominance of degenerative factors results in cartilage damage and the development of osteoarthritis (OA). An increased density of macrophages in association with the increased expression of mediators of inflammation in degenerating cartilage of vitamin D-deficient microswine and the association of vitamin D supplementation with decreased macrophages and increased triggering receptor expressed on myeloid cells (TREM)-2 expression, an anti-inflammatory receptor, have been reported previously by us [1]. These results suggest the presence of inflammation and macrophages in osteoarthritic cartilage

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