OBJECTIVE -Wound healing is known to require a well-organized balance of numerous factors, e.g., cytokines, matrix metalloproteinases (MMPs), and their inhibitors, as well as direct cell-cell communication (connexins). Disruption of this balance may lead to the formation of chronic wounds such as diabetic foot ulcers. The transplantation of autologous keratinocytes is a promising therapy for diabetic foot ulcers; however, little is known about their characteristics on a molecular level. Therefore, we intended to characterize transplanted keratinocytes from diabetic and nondiabetic origin before and after transplantation.RESEARCH DESIGN AND METHODS -We isolated human keratinocytes from diabetic and nondiabetic origins and transplanted them into an ex vivo wound healing model. To characterize the keratinocytes, we investigated mRNA expression of MMP-1, MMP-2, and MMP-9; tissue inhibitor of MMP (TIMP)-1 and TIMP-2; interleukin (IL)-1, tumor necrosis factor (TNF)-␣; Cx26 (connexin 26) and Cx43; and, for connexins, immunolocalization.RESULTS -We found no significantly increased expression of the molecules investigated in cultured keratinocytes from diabetic compared with nondiabetic origin, even though there were significant differences for MMP-2, IL-1, and TNF-␣ in skin biopsies. Expression of IL-1 was significantly lower in keratinocytes from diabetic origin. In the course of wound healing, differences in the dynamics of expression of MMP-1, IL-1, and Cx43 were observed.CONCLUSIONS -Our results suggest that keratinocytes from diabetic origin are as capable for transplantation into chronic wounds as keratinocytes from healthy origin at the starting point of therapy. However, differences in expression dynamics later on might reflect the systemic influence of diabetes resulting in a memory of the transplanted keratinocytes. Diabetes Care 31:114-120, 2008D iabetic foot syndrome represents a major complication of diabetes causing considerable mortality and substantial lower-limb amputation rates of about 44,000 per year in Germany (1).To comprehend the microenvironment of acute and chronic wounds, the pathophysiology of impaired wound healing has been increasingly investigated. Elevated levels of matrix metalloproteinases (MMPs) and reduced levels of their endogenous tissue inhibitors (tissue inhibitors of MMP [TIMPs]) have been shown in chronic wounds, including diabetic foot lesions, and can result in excessive proteolysis of tissue, as well as of growth factors and their receptors (2-4). MMPs are responsible for controlled degradation of the extracellular matrix as well as migration in normal wound healing. They also affect angiogenesis and remodeling of the dermis. MMPs are produced by several types of cells including fibroblasts, keratinocytes, macrophages, and eosinophils.Inflammatory cytokines, such as interleukin (IL)-1 and tumor necrosis factor (TNF)-␣ (5), have also been shown to be increased in nonhealing wounds. They stimulate synthesis and secretion of MMPs but inhibit the production of TIMPs (6,7). In...
Our study demonstrates that the TAPP learning curve of young trainees is only related to operation time. Therefore, TAPP is a safe and reproducible technique when performed by young trainees under the supervision of experienced laparoscopic surgeons. With an adequate program, the technique can be learned quickly, skillfully, and safely when a standardized technique is used. It should be included as a fundamental part of state-of-the-art trainee programs.
CE decreases expression of mast cell-specific mediators in vitro and in vivo and thus is a new plant-originated candidate for anti-allergic therapy.
SummaryMast cells are now considered sentinels in immunity. Given their location underneath the gastrointestinal barrier, mast cells are entrusted with the task of tolerating commensal microorganisms and eliminating potential pathogens in the gut microbiota. The aim of our study was to analyse the responsiveness of mast cells isolated from macroscopically normal and Crohn's disease-affected intestine to lipopolysaccharide (LPS). To determine the LPS-mediated signalling, human intestinal mast cells were treated with LPS alone or in combination with soluble CD14 due to their lack of surface CD14 expression. LPS alone failed to stimulate cytokine expression in human intestinal mast cells from both macroscopically normal and Crohn's disease tissue. Upon administration of LPS and soluble CD14, there was a dose-and time-dependent induction of cytokine and chemokine expression. Moreover, CXCL8 and interleukin-1b protein expression was induced in response to activation with LPS plus soluble CD14. Expression of cytokines and chemokines was at similar levels in mast cells from macroscopically normal and Crohn's disease-affected intestine after LPS/soluble CD14 treatment. In conclusion, human intestinal mast cells appear to tolerate LPS per se. The LPS-mediated activation in mast cells may be provoked by soluble CD14 distributed by other LPStriggered cells at the gastrointestinal barrier.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.