Howard G. Welgus

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We studied the role of the matrix metalloproteinase gelatinase B (gelB; MMP-9) in epithelial regeneration using the gelB-deficient mouse. We report the novel finding that, in contrast to other MMPs expressed at the front of the advancing epithelial sheet in wounds of cornea, skin, or trachea, gelB acts to inhibit the rate of wound closure. We determined(More)
Angiostatin, a cleavage product of plasminogen, has been shown to inhibit endothelial cell proliferation and metastatic tumor cell growth. Recently, the production of angiostatin has been correlated with tumor-associated macrophage production of elastolytic metalloproteinases in a murine model of Lewis lung cell carcinoma. In this report we demonstrate that(More)
Macrophages are present in inflammatory tissue sites where abnormal degradation of the extracellular matrix takes place. To evaluate the potential of macrophages to participate in such matrix destruction, we studied the effects of three cytokines present in inflammatory tissue sites, TNF-alpha, IL-1beta, and IFN-gamma, on the production of three(More)
Human mononuclear phagocytes can modulate the turnover of extracellular matrix by producing metalloproteinases such as 92-kD gelatinase and interstitial collagenase as well as the tissue inhibitor of metalloproteinases (TIMP). We have previously reported that IL-4 and IFN gamma released by lymphocytes suppress metalloproteinase biosynthesis in macrophages(More)
Osteoclasts form an acidic compartment at their attachment site in which bone demineralization and matrix degradation occur. Although both the cysteine proteinases and neutral collagenases participate in bone resorption, their roles have remained unclear. Here we show that interstitial collagenase has an essential role in initiating bone resorption,(More)
We have shown in a variety of human wounds that collagenase-1 (MMP-1), a matrix metalloproteinase that cleaves fibrillar type I collagen, is invariably expressed by basal keratinocytes migrating across the dermal matrix. Furthermore, we have demonstrated that MMP-1 expression is induced in primary keratinocytes by contact with native type I collagen and not(More)
OBJECTIVE To characterize the clinical and histopathologic changes in a rat model of broad-spectrum matrix metalloproteinase (MMP)-induced musculoskeletal syndrome (MSS), and to facilitate research into the causes and treatments of MSS in humans. METHODS Male Lewis rats weighing 150-180 gm were administered 10-30 mg of the broad-spectrum MMP inhibitor(More)
Wound repair involves cell migration and tissue remodeling, and these ordered and regulated processes are facilitated by matrix-degrading proteases. We reported that interstitial collagenase is invariantly expressed by basal keratinocytes at the migrating front of healing epidermis (Saarialho-Kere, U. K., E. S. Chang, H. G. Welgus, and W. C. Parks, 1992. J.(More)
We reported that interstitial collagenase is produced by keratinocytes at the edge of ulcers in pyogenic granuloma, and in this report, we assessed if production of this metalloproteinase is a common feature of the epidermal response in a variety of wounds. In all samples of chronic ulcers, regardless of etiology, and in incision wounds, collagenase mRNA,(More)
We report that matrilysin, a matrix metalloproteinase, is constitutively expressed in the epithelium of peribronchial glands and conducting airways in normal lung. Matrilysin expression was increased in airway epithelial cells and was induced in alveolar type II cells in cystic fibrosis. Other metalloproteinases (collagenase-1, stromelysin-1, and 92-kD(More)