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Interactions among three molecules generated from leukocytes and/or epithelial cells, elastase, PEPI and SLPI mediates the host defense and wound repair. Results rveal that SLPI/elastase act through PEPI/epithelins to operate a switch found at the interface between innate immunity and wound healing.

Author(s): Gillian S. Ashcroft [1, 3]; Kejian Lei [1, 3]; Wenwen Jin [1]; Glenn Longenecker [2]; Ashok B. Kulkarni [2]; Teresa Greenwell-Wild [1]; Hollie Hale-Donze [1]; George McGrady [1]; Xiao-Yu [...]

Impaired wound healing states lead to substantial morbidity and cost with treatment resulting in an expenditure of billions of dollars per annum in the US alone. Both chronic wounds and impaired acute wounds are characterized by excessive inflammation, enhanced proteolysis, and reduced matrix deposition. These confounding factors are exacerbated in the elderly, in part, as we report here, related to increased local and systemic tumor necrosis factor-alpha ( TNF-α) levels. Moreover, we have used a secretory leukocyte protease inhibitor ( SLPI) null mouse model of severely impaired wound healing and excessive inflammation, comparable to age-related delayed human healing, to demonstrate that topical application of anti- TNF-α neutralizing antibodies blunts leukocyte recruitment and NFκB activation, alters the balance between M1 and M2 macrophages, and accelerates wound healing. Following antagonism of TNF-α, matrix synthesis is enhanced, associated with suppression of both inflammatory parameters and NFκB binding activity. Our data suggest that inhibiting TNF-α is a critical event in reversing the severely impaired healing response associated with the absence of SLPI, and may be applicable to prophylaxis and/or treatment of impaired wound healing states in humans. [ABSTRACT FROM AUTHOR]

Expression of endogenous transforming growth factor-β1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-β has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-β1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-β1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3–10-day-old neonatal transforming growth factor-β1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-β1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-β1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-β1 null mice. Again, no impairment in healing was seen in transforming growth factor-β1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-β1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-β1 may actually function to increase inflammation and retard wound closure. [ABSTRACT FROM AUTHOR]

Presents information on the immune system as it relates to ageing. Background information on the studies of the ageing immune system; Details on what the nature of immunity; Description of the effects of human ageing.

Studies the association between elastin gene mutation and the production of abnormal tropoelastin and abnormal elastic fibers in patients with autosomal dominant cutis laxa. Characteristic structures of hydrophobic and cross-linking domains; Effect of intermolecular cross-link formation on tropoelastin alignment in microfibrils.

Presents letters related to medical research. Scandal of poor medical research; Pressure in doing researches; Deception of scientific mantles by doctors.