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

Department of Translational Research, Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA
*
Author to whom correspondence should be addressed.
This is part of Vikrant Rai’s doctoral thesis.
Academic Editor: Scott Alper
Received: 27 August 2021 / Revised: 14 October 2021 / Accepted: 22 October 2021 / Published: 26 October 2021
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. View Full-Text
Keywords: cartilage degeneration; osteoarthritis; inflammation; interleukin-33; interleukin-37; vitamin D supplementation; macrophage polarization cartilage degeneration; osteoarthritis; inflammation; interleukin-33; interleukin-37; vitamin D supplementation; macrophage polarization
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MDPI and ACS Style

Rai, V.; Radwan, M.M.; Agrawal, D.K. IL-33, IL-37, and Vitamin D Interaction Mediate Immunomodulation of Inflammation in Degenerating Cartilage. Antibodies 2021, 10, 41. https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040041

AMA Style

Rai V, Radwan MM, Agrawal DK. IL-33, IL-37, and Vitamin D Interaction Mediate Immunomodulation of Inflammation in Degenerating Cartilage. Antibodies. 2021; 10(4):41. https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040041

Chicago/Turabian Style

Rai, Vikrant, Mohamed M. Radwan, and Devendra K. Agrawal. 2021. "IL-33, IL-37, and Vitamin D Interaction Mediate Immunomodulation of Inflammation in Degenerating Cartilage" Antibodies 10, no. 4: 41. https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040041

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