Human α defensins promote the expression of the inflammatory cytokine interleukin‐8 under high‐glucose conditions: Novel insights into the poor healing of diabetic foot ulcers

• Published in: Journal of biochemical and molecular toxicology 2019-08, Vol.33 (8), p.e22351-n/a
• Main Authors: Meng, Lanxia, Guo, Xingchen, Yang, Xilin, Liu, Hongyue, Yu, Mosheng, Wu, Yingliang, Zhu, Zhanyong
• Format: Article
• Language: English
• Subjects: Adult; advanced glycation end products; Advanced glycosylation end products; alpha-Defensins - chemistry; alpha-Defensins - physiology; Amino Acid Sequence; Bovine serum albumin; Chronic infection; Cytokines; Defensins; Diabetes; Diabetes mellitus; Diabetic Foot - metabolism; Diabetic Foot - physiopathology; diabetic foot ulcer; Exudates; Exudation; Feet; Female; Fibroblasts; Foot diseases; Glucose - administration & dosage; Glycosylation; Healing; Hemoglobin; human α defensins; Humans; Inflammation; Inflammation Mediators - metabolism; Inflammatory response; Interleukin-8 - metabolism; Interleukins; interleukin‐8; Leg ulcers; Male; Middle Aged; Serum albumin; synergistic effect; Ulcers; Wound Healing; Wounds
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.22351

Sustained infection and chronic inflammation are the most common features and complex mechanisms of diabetic foot disease. In this study, we examined the expression and functional roles of human endogenous α defensins in diabetic foot ulcer. The expression levels of human α defensins HNP1, HNP3, and HNP4 were significantly higher in the wound center than the edge of diabetic foot ulcers. And the inflammatory cytokine interleukin IL‐8 (IL‐8) was also highly expressed in wound exudates. In human foreskin fibroblasts, these human α defensins were found only slightly to affect IL‐8 expression directly. hemoglobin A1C (HbA1c) is the main clinical indicator of diabetic foot disease. Advanced glycation end products of bovine serum albumin (AGE‐BSA), as HbA1c analogue, was found to promote IL‐8 expression. Human α defensins, in the presence of AGE‐BSA, further significantly promoted IL‐8 expression. These findings showed that human α defensins aggravated the inflammatory response in diabetic foot ulcers patients, providing new insights in to the poor healing of diabetic foot ulcers.