Counteractive Effects of IL-33 and IL-37 on Inflammation in Osteoarthritis

Vikrant Rai, Matthew F. Dilisio, Farial Samadi and Devendra K. Agrawal
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Vikrant Rai: Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA
Matthew F. Dilisio: Department of Orthopedic Surgery, Creighton University School of Medicine, Omaha, NE 68178, USA
Farial Samadi: Department of Biology, College of Arts and Sciences, University of Nebraska at Omaha, Omaha, NE 68182, USA
Devendra K. Agrawal: Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA

IJERPH, 2022, vol. 19, issue 9, 1-21

Abstract: Osteoarthritis (OA) is a chronic inflammatory disease where pro-inflammatory cytokines, damage-associated molecular patterns (DAMPs), and macrophages play a crucial role. However, the interactive role of these mediators, the exact cause precipitating OA and definitive treatment for OA are not known yet. Moreover, the interactive role of interleukin (IL)-33 and IL-37 with other factors in the pathogenesis of OA has not been discussed elaborately. In this study, we analyzed the expression of IL-33 and IL-37 in human OA knee and hip joint cartilage tissues. The effect of increased DAMPs, IL-33, and IL-37 on IL-6, tumor necrosis factor (TNF)-α, toll-like receptors (TLRs), and matrix metalloproteinases (MMPs) expression was delineated using human normal and osteoarthritic chondrocytes. The effect of anti-inflammatory cytokine IL-37 on various mediators of inflammation in the presence of IL-33, rHMGB-1, and LPS was investigated to delineate the effects of IL-37. Further, the effects of blocking IL-33 downstream signaling and the effects of IL-33 and IL-37 on macrophage polarization were assessed along with examining the macrophage phenotypes in human OA cartilage tissues. The results of this study revealed increased expression of IL-33 in OA cartilage and that IL-33 increases IL-6, TNF-α, TLRs, and MMPs expression and favors phenotypic conversion towards the M1 phenotype, while IL-37 and blocking IL-33 receptor ST2 have opposite effects. Overall, the results suggest that blocking IL-33 and increasing IL-37 act synergistically to attenuate inflammation and might serve as potential therapeutics in OA.

Keywords: osteoarthritis; inflammation; damage-associated molecular patterns; Interleukin-33; Interleukin-37; Toll-like receptors; matrix metalloproteinases; Macrophages (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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