NLRP3 Inflammasome Expression and Signaling in Human Diabetic Wounds and in High Glucose Induced Macrophages.
Introduction.To investigate the contribution and mechanism of NLRP3 inflammasome expression in human wounds in diabetes mellitus and in high glucose induced macrophages.Methods.In the present study, we compared the expression of NLRP3 inflammasome in debridement wound tissue from diabetic and nondiabetic patients. We also examined whether high glucose induces NLRP3 inflammasome expression in cultures THP-1-derived macrophages and the influence on IL-1βexpression.Results.The expressions of NLRP3, caspase1, and IL-1β, at both the mRNA and protein level, were significantly higher in wounds of diabetic patients compared with nondiabetic wounds (P< 0.05). High glucose induced a significant increase in NLRP3 inflammasome and IL-1βexpression in THP-1-derived macrophages. M1 macrophage surface marker with CCR7 was significantly upregulated after high glucose stimulation. SiRNA-mediated silencing of NLRP3 expression downregulates the expression of IL-1β.Conclusion.The higher expression of NLRP3, caspase1, and secretion of IL-1β, signaling, and activation might contribute to the hyperinflammation in the human diabetic wound and in high glucose induced macrophages. It may be a novel target to treat the DM patients with chronic wound.
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Jiao Tong University, Shanghai, China.
Xiaotian
X
Zhang
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Jiao Tong University, Shanghai, China.
Jiezhi
J
Dai
Department of Orthopedic Surgery, Shanghai First People's Hospital, Jiao Tong University, Shanghai, China.
Li
L
Li
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Jiao Tong University, Shanghai, China.
Hua
0000-0003-4323-6403
H
Chen
Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Jiao Tong University, Shanghai, China.
Yimin
0000-0002-1972-5971
Y
Chai
D000328:Adult; D020170:Caspase 1 / Q000378:metabolism; D017719:Diabetic Foot / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020170:Caspase 1; D005947:Glucose