A5048524904- Skin Protection and Aging
- Inflammatory mediators and NSAID effects
- Wound Healing and Treatments
- Dermatology and Skin Diseases
- Nonmelanoma Skin Cancer Studies
- Medicine and Dermatology Studies History
- Effects of Radiation Exposure
- Protease and Inhibitor Mechanisms
- Chemotherapy-related skin toxicity
- Skin and Cellular Biology Research
- Cell Adhesion Molecules Research
- Estrogen and related hormone effects
- Autoimmune Bullous Skin Diseases
- NF-κB Signaling Pathways
- Cutaneous Melanoma Detection and Management
- Dupuytren's Contracture and Treatments
- Urticaria and Related Conditions
- Drug-Induced Adverse Reactions
- Healthcare Systems and Technology
- Psoriasis: Treatment and Pathogenesis
- Mast cells and histamine
- Nail Diseases and Treatments
- Genomics, phytochemicals, and oxidative stress
- Contact Dermatitis and Allergies
- Redox biology and oxidative stress
University of Rochester Medical Center
2014-2025
University of Rochester
2013-2025
State Innovation Exchange
2023
In-Q-Tel
2023
Pfizer (United Kingdom)
2022
Sanofi (Mexico)
2022
Regeneron (United States)
2022
Estée Lauder (United States)
2022
Bristol-Myers Squibb (Germany)
2022
Janssen (Belgium)
2022
We present a cascade of proteolytic events catalyzed by the proteases secreted cultured keratinocytes and fibroblasts that results in activation interstitial procollagenase. Cultured human skin constitutively secrete collagenase stromelysin as proenzymes. In contrast, found serum-free organ culture conditioned medium is activated. Cocultivation major cellular components culture, dermal epidermal keratinocytes, induces procollagenase prostromelysin presence plasminogen. This occurs through...
Ultraviolet radiation (UVR) has widespread effects on the biology and integrity of skin barrier. Research mechanisms that drive these changes, as well their effect barrier function, been ongoing since 1980s. However, no studies have examined impact UVR nanoparticle penetration. Nanoparticles (NP) are commonly used in sunscreens other cosmetics, consumer use sunscreen is often applied to sun damaged skin, NP penetration a concern due potential toxicity. In this study, we investigate by...
Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability curcumin reduce radiation severity 30 cancer patients. Eligible were adult females with noninflammatory or carcinoma situ prescribed RT without concurrent chemotherapy. Randomized took 2.0 grams placebo orally three times per day (i.e., 6.0 daily) throughout their course RT. Weekly...
UV light is a complete carcinogen, inducing both basal and squamous cell skin cancers. The work described uses the selective COX-2 inhibitor celecoxib to examine efficacy of inhibition in reduction light-induced tumor formation hairless mice. UVA-340 sun lamps were chosen as source that effectively mimics solar UVA UVB spectrum. Hairless mice irradiated for 5 days week total dose 2.62 J/cm2. When 90% animals had at least one tumor, divided into two groups so number multiplicity same (P <...
We reported that interstitial collagenase is produced by keratinocytes at the edge of ulcers in pyogenic granuloma, and this report, we assessed if production metalloproteinase a common feature epidermal response variety wounds. In all samples chronic ulcers, regardless etiology, incision wounds, mRNA, localized situ hybridization, was prominently expressed basal bordering sites active re-epithelialization indicating collagenolytic activity characteristic epidermis to wounding. No expression...
The mitogen-activated protein kinase (MAPK) cascade is believed to function as an important regulator of prostaglandin biosynthesis. Previously we reported that interleukin-1β induces activation JNK/SAPK and p38 MAPK with concomitant up-regulation cyclooxygenase (Cox)-2 expression E<sub>2</sub> (PGE<sub>2</sub>) synthesis. Our experiments demonstrate overexpression ΔMEKK1 (a constitutively active truncation mutant MEKK1 containing the C-terminal 324 amino acids) increases Cox-2...
Wound repair involves cell migration and tissue remodeling, these ordered regulated processes are facilitated by matrix-degrading proteases. We reported that interstitial collagenase is invariantly expressed basal keratinocytes at the migrating front of healing epidermis (Saarialho-Kere, U. K., E. S. Chang, H. G. Welgus, W. C. Parks, 1992. J. Clin. Invest. 90:1952-1957). Because limited substrate specificity collagenase, principally for fibrillar collagens, other enzymes must also be...
BackgroundPreclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated efficacy and safety of celecoxib, a inhibitor, as chemopreventive agent for actinic keratoses, premalignant precursor nonmelanoma cancers, including cutaneous squamous cell carcinomas (SCCs) basal (BCCs).
To understand the relationship between proliferation of epidermis and its arachidonic acid metabolism, we studied human keratinocytes grown in vitro at confluent or nonconfluent densities. Keratinocyte cultures incubated with [14C]arachidonic synthesized prostaglandin (PG)E2 PGD2, PGF2 alpha, small quantities 6-keto-F1 alpha. Nonconfluent cultures, however, fourfold more PGE2 than did cultures. When was using [3H]thymidine incorporation into DNA, it found that this increased synthesis...
To study the signal transduction mechanisms by which ultraviolet B (UVB) leads to increased prostaglandin E2 (PGE2) synthesis, human epidermal cultures were irradiated with 30 mJ/cm2 UVB and assayed for 6-h cumulative PGE2. Supernatants from showed a 4-fold increase in PGE2 synthesis (113.6 +/- 26.8 pg/mg protein) when compared supernatants sham-irradiated (25.6 3.9 protein). Pretreatment of genistein (10 micrograms/ml) or tyrphostin-23 (50 microM), inhibitors tyrosine kinases, blocked...
The pathogenic gram-positive bacterium Streptococcus pyogenes (group A streptococcus) causes numerous diseases of cutaneous tissue, each which is initiated after the interaction with cells epidermis. In this study, we show that different surface proteins S. play important roles in determining cell-specific tropism skin. Using streptococcal strains defined mutations genes encode combination primary cultures human skin and an situ adherence assay uses histological sections skin, M protein...
Many cellular properties are influenced by the surrounding environment of extracellular matrix. To better define interaction between mononuclear phagocytes and matrix components they contact, we studied effect various matrices on biosynthesis secretion metalloenzymes tissue inhibitor metalloproteinases in human alveolar macrophages. We found that native denatured collagen types I III markedly augmented production interstitial collagenase (> 25-fold) increased to a lesser degree (2.5-fold)....
Acute ultraviolet light B (UVB) injury is associated with dermal mast cell histamine release. The possibility that histamine-stimulated prostaglandin (PG) synthesis could be a mechanism for irradiation erythema was therefore examined using human skin explants. Explants responded to UV (120 mJ/cm2) fivefold increase in of prostaglandins E2, F2 alpha and 6-keto PGF1 alpha. Incubating explants the H1 antihistamines brompheniramine (50 microM) or pyrilamine (30 inhibited PG release from...
Human epidermal cells exhibited none of the cytosolic lipoxygenase activity that is prominent in mucosal epithelial cells, but instead contained a microsomal converted arachidonic acid to 12-hydroxyeicosatetraenoic (12-HETE). Identification extractable 12-HETE-forming as 12-lipoxygenase (distinct from cytochrome P-450) included (S)-12-stereospecificity product formation, trapping 12-hydroperoxyeicosatetraenoic an intermediate reaction product, and lack NADPH dependence for activity....
In contrast to a mutant adhesin-deficient Streptococcus pyogenes (group A streptococcus), its isogenic parental strain binds human keratinocytes and promotes vigorous proinflammatory response, characterized by enhanced expression of several cytokines, more rapid release prostaglandin E2 (PGE2) damage keratinocyte membranes. However, adherence alone is not sufficient induce these responses. this study, we have begun examine the contribution other streptococcal products in interactions with...
We have previously shown that during wound healing migrating keratinocytes, which are in contact with the dermal matrix, express interstitial collagenase, whereas basal epidermal cells, reside on an intact basement membrane, do not. Duplicating this vivo pattern, collagenase production was induced primary human keratinocytes grown native type I collagen, but only background levels of enzyme were detected cells cultured denatured collagen or Matrigel. Using genistein, herbimycin A, and sodium...