Dietary zinc alters early inflammatory responses during cutaneous wound healing in weanling CD-1 mice.
Zinc deficiency is a well-known health problem associated with delayed wound healing, yet the precise mechanisms that underlie the delay remain unknown. We hypothesized that zinc deficiency delays wound healing as a result of decreased nuclear factor (NF)kappaB activation, reduced expression of proinflammatory cytokines [interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha], and a decrease in neutrophil infiltration during the early stage of cutaneous wound healing. We used a cutaneous, full-thickness excisional wound model in CD-1 mice to examine the rate of wound closure as well as mRNA levels of inhibitory (I)kappaBalpha, IL-1beta, and TNF-alpha and infiltration of neutrophils at the wound site of mice fed a diet containing <1 (deficient), 50 (control), 500, or 1000 microg zinc/g diet. Zinc deficiency reduced the rate of wound closure and mRNA levels of IL-1beta and TNF-alpha and attenuated infiltration of neutrophils at the wound site compared with controls. Interestingly, zinc supplementation at 1000 microg/g delayed the rate of wound closure and decreased mRNA levels of TNF-alpha and infiltration of neutrophils compared with mice fed the control diet. These findings demonstrate that zinc deficiency and high-dose zinc supplementation delay wound healing as a result of altered inflammatory responses and suggest that adequate zinc supplementation may have beneficial effects on the inflammatory responses to enhance cutaneous wound healing.
Lim
Yunsook
Y
Department of Human Nutrition, The Ohio State University, Columbus, OH, USA.
Levy
Mark
M
Bray
Tammy M
TM
D000818:Animals; D001835:Body Weight; D004032:Diet; D004435:Eating; D005260:Female; D020672:I-kappa B Proteins / Q000235:genetics; D007249:Inflammation / Q000473:pathology / Q000628:therapy*; D007375:Interleukin-1 / Q000235:genetics; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D009504:Neutrophils / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000293:injuries*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014886:Weaning; D014945:Wound Healing; D015032:Zinc / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood
D020672:I-kappa B Proteins; D007375:Interleukin-1; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D015032:Zinc