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

Vikrant Rai, Matthew F. Dilisio, Farial Samadi, Devendra K. Agrawal

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number5690
JournalInternational Journal of Environmental Research and Public Health
Volume19
Issue number9
DOIs
StatePublished - May 1 2022

All Science Journal Classification (ASJC) codes

  • Pollution
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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