The Effect of Heparin and Other Exogenous Glycosaminoglycans (GAGs) in Reducing IL-1β-Induced Pro-Inflammatory Cytokine IL-8 and IL-6 mRNA Expression and the Potential Role for Reducing Inflammation

Murtaza Jafri; Lin Li; Binhua Liang; Ma Luo

doi:10.3390/ph17030371

The Effect of Heparin and Other Exogenous Glycosaminoglycans (GAGs) in Reducing IL-1β-Induced Pro-Inflammatory Cytokine IL-8 and IL-6 mRNA Expression and the Potential Role for Reducing Inflammation

Pharmaceuticals (Basel). 2024 Mar 14;17(3):371. doi: 10.3390/ph17030371.

Authors

Murtaza Jafri¹, Lin Li², Binhua Liang^{2

3}, Ma Luo^{2

4}

Affiliations

¹ Faculty of Medicine, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
² National Microbiology Laboratory, Winnipeg, MB R3E 3R2, Canada.
³ Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
⁴ Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.

Abstract

Glycosaminoglycans (GAGs) are long linear polysaccharides found in every mammalian tissue. Previously thought only to be involved in cellular structure or hydration, GAGs are now known to be involved in cell signaling and protein modulation in cellular adhesion, growth, proliferation, and anti-coagulation. In this study, we showed that GAGs have an inhibitory effect on the IL-1β-stimulated mRNA expression of IL-6 and IL-8. Exogenous heparin (p < 0.0001), heparan (p < 0.0001), chondroitin (p < 0.049), dermatan (p < 0.0027), and hyaluronan (p < 0.0005) significantly reduced the IL-1β-induced IL-8 mRNA expression in HeLa cells. Exogenous heparin (p < 0.0001), heparan (p < 0.0001), and dermatan (p < 0.0027) also significantly reduced IL-1β-induced IL-6 mRNA expression in HeLa cells, but exogenous chondroitin and hyaluronan had no significant effect. The exogenous GAGs may reduce the transcription of these inflammatory cytokines through binding to TILRR, a co-receptor of IL-1R1, and block/reduce the interactions of TILRR with IL-1R1.

Keywords: IL-1β; IL-6; IL-8; glycosaminoglycans; heparin; inflammation.

Grants and funding

This research was funded and supported by the Dean of Max Rady College of Medicine, Rady Faculty of Health Sciences and A-based fund of National Microbiology Laboratory, Public Health Agency of Canada.