Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLR family pyrin domain containing 3 (NLRP3) inflammasome in diabetic rats.

Abstract

BACKGROUND:

Heparan sulfate (HS) attenuates the inflammatory response and improves diabetic wound healing in rats. However, the specific mechanisms by which HS suppresses inflammation are not clear. Given that NLR family pyrin domain containing 3 (NLRP3) is a major receptor involved in innate immune regulation, the aim of the present study was to elucidate the effects of HS on NLRP3 and proinflammatory cytokines in diabetic wounds.

METHODS:

Full-thickness wounds were created on the back of diabetic rats. The experimental group received HS treatment (1 mg/kg, i.m., on Days 0 and 7), whereas the control group received vehicle (0.1% dimethylsulfoxide in 0.9% NaCl). Expression of NLRP3 and its downstream effector molecules, namely cleaved interleukin (IL)-1β, IL-18, tumor necrosis factor (TNF)-α, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), proteinase inhibitor 9, and caspase-12, in the wound tissues was examined.

RESULTS:

Treatment with HS accelerated wound healing in diabetic rats. Rats treated with HS exhibited decreased activation of cleaved IL-1β, IL-18, and TNF-α, as well as decreased expression of NLRP3 and ASC. In addition, HS increased levels of proteinase inhibitor 9 and caspase-12.

CONCLUSIONS:

Heparan sulfate inhibits inflammation and improves wound healing by downregulating the NLRP3 inflammasome and cleaved IL-1β during the wound healing process in diabetic rats.

• Authors: Tao Wang, Jun Zhao, Jian Zhang, Jiacai Mei, Mingzhe Shao, Ye Pan, Wenchao Yang, Yujie Jiang, Fang Liu, Weiping Jia
• Journal: Journal of diabetes (J Diabetes) Vol. 10 Issue 7 Pg. 556-563 (Jul 2018) ISSN: 1753-0407 [Electronic] Australia
• PMID: 29171721 (Publication Type: Journal Article)
• Copyright: © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Chemical References

• Cytokines
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Heparitin Sulfate

Topics

• Animals
• Apoptosis (drug effects)
• Cytokines (metabolism)
• Diabetes Mellitus, Experimental (complications, physiopathology)
• Heparitin Sulfate (pharmacology)
• Inflammasomes (drug effects)
• Inflammation (drug therapy, etiology)
• Male
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors)
• Rats
• Rats, Sprague-Dawley
• Wound Healing (drug effects)