Treatment of diabetic mice with undenatured whey protein accelerates the wound healing process by enhancing the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-β in wounded tissue

Gamal Badr,Danny M Rabah,Mohamed Mohany,Olivier Garraud,Badr M Badr,Mohamed H Mahmoud

doi:10.1186/1471-2172-13-32

Abstract

BackgroundContinuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection. Diabetes can cause poor circulation in the feet, increasing the likelihood of ulcers forming when the skin is damaged and slowing the healing of the ulcers. Whey proteins (WPs) enhance immunity during childhood and have a protective effect on some immune disorders. Therefore, in this study, we investigated the effects of camel WP on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced type I diabetic mouse model.ResultsDiabetic mice exhibited delayed wound closure characterized by a significant decrease in an anti-inflammatory cytokine (namely, IL-10) and a prolonged elevation of the levels of inflammatory cytokines (TNF-α, IL-1β and IL-6) in wound tissue. Moreover, aberrant expression of chemokines that regulate wound healing (MIP-1α, MIP-2, KC and CX3CL1) and growth factors (TGF-β) were observed in the wound tissue of diabetic mice compared with control nondiabetic mice. Interestingly, compared with untreated diabetic mice, supplementation with WP significantly accelerated the closure of diabetic wounds by limiting inflammatory stimuli via the restoration of normal IL-10, TNF-α, IL-1β and IL-6 levels. Most importantly, the supplementation of diabetic mice with WP significantly modulated the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-β in wound tissue compared with untreated diabetic mice.ConclusionOur data demonstrate the benefits of WP supplementation for improving the healing and closure of diabetic wounds and restoring the immune response in diabetic mice.

Highlights

Continuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection
CX3CL1 directly stimulates angiogenesis, the local microvasculature depends on several other growth factors, including transforming growth factor-β (TGF-β), which is produced by macrophages in wounds [15] and functions in leukocyte chemotaxis, fibroblast and smooth muscle cell mitogenesis and extracellular matrix deposition during granulation tissue formation [16]
Administration of camel Whey proteins (WPs) expedites wound closure in diabetic mice We evaluated the macroscopic changes at skin-excision wound sites in control mice, diabetic mice and diabetic mice supplemented with WP

Summary

Introduction

Continuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection. Impaired wound healing represents a severe complication of the disease, which could diminish physical activity and lead status of the individual [6]. Cytokines such as IL-1α, IL-1β, IL-6, and TNF-α are thought to play important roles in wound repair, including the stimulation of keratinocyte and fibroblast proliferation, the synthesis and breakdown of extracellular matrix proteins, fibroblast chemotaxis, and immune response regulation [7]. CX3CL1 directly stimulates angiogenesis, the local microvasculature depends on several other growth factors, including transforming growth factor-β (TGF-β), which is produced by macrophages in wounds [15] and functions in leukocyte chemotaxis, fibroblast and smooth muscle cell mitogenesis and extracellular matrix deposition during granulation tissue formation [16]

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