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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.

Badr G, Badr BM, Mahmoud MH, Mohany M, Rabah DM, Garraud O - BMC Immunol. (2012)

Bottom Line: Continuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection.Whey proteins (WPs) enhance immunity during childhood and have a protective effect on some immune disorders.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Princes Johara alibrahim center for cancer research, prostate cancer research chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia. badr73@yahoo.com

ABSTRACT

Background: Continuous 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.

Results: Diabetic 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.

Conclusion: Our data demonstrate the benefits of WP supplementation for improving the healing and closure of diabetic wounds and restoring the immune response in diabetic mice.

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Profile of pro- and anti-inflammatory cytokines in wound area. Thelevels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6)and an anti-inflammatory cytokine (IL-10) were measured by ELISA in thewound tissues from the 3 groups of mice before wounding (Day 0) and onthe indicated days post-wounding. The results are expressed as themean ± SEM. *P < 0.05,diabetic vs. control; +P < 0.05,diabetic + WP vs. control;#P < 0.05, diabetic + WP vs.diabetic (ANOVA with Tukey’s post-test).
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Figure 2: Profile of pro- and anti-inflammatory cytokines in wound area. Thelevels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6)and an anti-inflammatory cytokine (IL-10) were measured by ELISA in thewound tissues from the 3 groups of mice before wounding (Day 0) and onthe indicated days post-wounding. The results are expressed as themean ± SEM. *P < 0.05,diabetic vs. control; +P < 0.05,diabetic + WP vs. control;#P < 0.05, diabetic + WP vs.diabetic (ANOVA with Tukey’s post-test).

Mentions: Cytokines are secreted by specific immune cells, carry signals locally betweencells and are critical for the wound healing process. Therefore, we monitoredthe levels of pro- and anti-inflammatory cytokines that control immune cellfunction during wound healing in the three groups of mice. Data from 10individual mice from each group are shown in Figure 2. We observed that the level of pro-inflammatory cytokines(TNF-α, IL-1β and IL-6) peaked at 4 days post-injury. Indiabetic mice, we observed aberrant and significantly elevated levels ofTNF-α, IL-1β and IL-6 compared with control and WP-treated diabeticmice from 4 to 13 days post-injury, which indicates a prolongedpro-inflammatory phase during the healing of diabetic wounds. By contrast, thelevel of IL-10 was significantly reduced in diabetic mice compared with controland WP-treated diabetic mice at the same time points. Thus, WP supplementationduring diabetes significantly restored the levels of TNF-α, IL-1β,IL-6 and IL-10.


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.

Badr G, Badr BM, Mahmoud MH, Mohany M, Rabah DM, Garraud O - BMC Immunol. (2012)

Profile of pro- and anti-inflammatory cytokines in wound area. Thelevels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6)and an anti-inflammatory cytokine (IL-10) were measured by ELISA in thewound tissues from the 3 groups of mice before wounding (Day 0) and onthe indicated days post-wounding. The results are expressed as themean ± SEM. *P < 0.05,diabetic vs. control; +P < 0.05,diabetic + WP vs. control;#P < 0.05, diabetic + WP vs.diabetic (ANOVA with Tukey’s post-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3676145&req=5

Figure 2: Profile of pro- and anti-inflammatory cytokines in wound area. Thelevels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6)and an anti-inflammatory cytokine (IL-10) were measured by ELISA in thewound tissues from the 3 groups of mice before wounding (Day 0) and onthe indicated days post-wounding. The results are expressed as themean ± SEM. *P < 0.05,diabetic vs. control; +P < 0.05,diabetic + WP vs. control;#P < 0.05, diabetic + WP vs.diabetic (ANOVA with Tukey’s post-test).
Mentions: Cytokines are secreted by specific immune cells, carry signals locally betweencells and are critical for the wound healing process. Therefore, we monitoredthe levels of pro- and anti-inflammatory cytokines that control immune cellfunction during wound healing in the three groups of mice. Data from 10individual mice from each group are shown in Figure 2. We observed that the level of pro-inflammatory cytokines(TNF-α, IL-1β and IL-6) peaked at 4 days post-injury. Indiabetic mice, we observed aberrant and significantly elevated levels ofTNF-α, IL-1β and IL-6 compared with control and WP-treated diabeticmice from 4 to 13 days post-injury, which indicates a prolongedpro-inflammatory phase during the healing of diabetic wounds. By contrast, thelevel of IL-10 was significantly reduced in diabetic mice compared with controland WP-treated diabetic mice at the same time points. Thus, WP supplementationduring diabetes significantly restored the levels of TNF-α, IL-1β,IL-6 and IL-10.

Bottom Line: Continuous diabetes-associated complications are a major source of immune system exhaustion and an increased incidence of infection.Whey proteins (WPs) enhance immunity during childhood and have a protective effect on some immune disorders.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Princes Johara alibrahim center for cancer research, prostate cancer research chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia. badr73@yahoo.com

ABSTRACT

Background: Continuous 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.

Results: Diabetic 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.

Conclusion: Our data demonstrate the benefits of WP supplementation for improving the healing and closure of diabetic wounds and restoring the immune response in diabetic mice.

Show MeSH
Related in: MedlinePlus