Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently established a mouse model for scleroderma by repeated local bleomycin treatment. In this study, we compared the susceptibility to bleomycin in the development of dermal sclerosis among Balb/c, C3H/He, C57BL/6J, A/J, DBA/2, B10.BR, B10.A, and B10.D2 mouse strains. After either bleomycin or PBS treatment, skin from the injection site was histologically examined. Dermal sclerosis was induced by bleomycin treatment for 4 weeks in all of the strains examined. In particular, C3H/He, DBA/2, B10.D2 and B10.A mice developed intense dermal sclerosis characterized by deposition of homogeneous material in the dermis and thickened collagen bundles. Dermal thickness showed a more than twofold increase following bleomycin treatment, as compared with PBS treatment, except in C57BL/6J and DBA/2 mice. In A/J, C3H/He, B10.A, and B10.D2 mice, dermal thickness showed a more than 2.5-fold increase. Mast cell numbers in sclerotic skin were significantly greater than in PBS-treated skin in Balb/c and B10.A mice after 4 weeks of treatment. We also examined whether bleomycin treatment for 3 weeks could induce dermal sclerosis in C3H mice. Histological examination revealed that epidermal thickness as well as dermal sclerosis was increased in C3H mice following bleomycin treatment for 3 weeks. Increased hydroxyproline content as well as mRNA expression of alpha1(I) collagen, as determined by Northern blot analysis, were observed following bleomycin treatment. Taken together, we conclude that C3H/He and B10.A mouse strains are bleomycin-'susceptible', and these strains are considered to be a suitable experimental model of bleomycin-induced scleroderma.
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PMID:Animal model of sclerotic skin. III: Histopathological comparison of bleomycin-induced scleroderma in various mice strains. 1119 91

Matrix degrading enzymes are implicated in several disease processes such as abdominal aortic aneurysms and emphysema, however, monitoring proteolytic activity in a single assay is not well-established. Numerous assays have been developed to measure matrix degrading enzymes, which use artificial substrates or substrates derived from natural substrate protein. We have recently developed an assay for elastolytic activity based on the detection of primary amines, using trinitrobenzene sulfonic acid (TNBSA), following the digestion of succinylated elastin. The assay is also versatile enough to allow the detection of other proteases through the use of succinylated substrate specific for given protease. In order to improve the sensitivity and versatility of the assay we have refined the buffer conditions (PBS pH 7.2/1 mM CaCl2) to provide a 60 % increase in sensitivity to elastolytic activity and also formulated a substrate mixture containing succinylated elastin, collagen and gelatin. The combination of a substrate mixture and an optimum buffer will allow a spectrum of enzymes to be detected in a single reaction, providing a more complete picture of total proteolytic activity in a biological sample. This assay may also provide a tool to use proteolytic activity as a marker to monitor pathologic conditions involving matrix turn-over.
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PMID:Single microassay for matrix degrading enzymes. 1128 68

Bullous pemphigoid is an autoimmune blistering skin disease characterized by IgG autoantibodies targeting the skin basement membrane component type XVII collagen (BPAg2). To gain understanding of the disease's induction phase, we subcutaneously immunized adult BALB/c mice with peptides of human and/or the murine-equivalent BPAg2 pathogenic NC16A domain. Female mice were injected with peptides (human, murine, or combined human and murine), or PBS control emulsified in CFA, on a four-week interval. At the fourth and subsequent immunizations, all peptide-immunized mice were given murine peptides. Two weeks after the sixth immunization, ELISA detected IgG circulating autoantibodies against self peptides in 92% (47/51) of mice immunized with murine peptides; whereas none of the preimmune sera or the sera from PBS control-immunized mice reacted to the self peptides. In four mice their autoantibodies labeled mouse skin basement membrane. Breaking B-cell tolerance to BPAg2 sets the first step in dissecting the disease's induction phase.
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PMID:Characterization of BALB/c mice B lymphocyte autoimmune responses to skin basement membrane component type XVII collagen, the target antigen of autoimmune skin disease bullous pemphigoid. 1137 4

DBA/1 mice immunized with 100 microg bovine collagen type II emulsified in Freund's adjuvant, followed by booster injection in incomplete adjuvant at 18 days, develop profound arthritis (>50% of animals) by 30 days postinjection. The molecule CD200 (previously called OX2), associated with, among others, follicular dendritic cells, is implicated in delivery of immunosuppressive signals to the immune system, and an immunoadhesin in which the extracellular domains of CD200 were linked to a mouse IgG2a Fc region has been shown to promote renal allograft survival. DBA/1 mice receiving 15 microg/mouse CD200Fc at 3-day intervals following immunization with collagen did not develop arthritis in this model. Lymphocytes taken from CD200Fc-treated, collagen-immunized mice produced significantly lower levels of TNFalpha and IFN-gamma in culture supernatants after restimulation in vitro with collagen, in contrast to cells taken from control mice treated with PBS or normal mouse Ig. Serum from CD200Fc-treated mice contained less anti-collagen IgG (approximately 50% reduction), with relatively more IgG2b and IgG3, and lower levels of TNFalpha and IFN-gamma, than control mice. These data indicate that this immunoadhesin may have a potent role to play in the regulation of autoimmune disorders.
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PMID:CD200 immunoadhesin suppresses collagen-induced arthritis in mice. 1172 25

Venom from Bothrops snake produces severe local symptoms on the envenomed victim, such as hemorrhage, edema and myonecrosis. The latter is perhaps the most important of all, since antivenom therapy is not effective for it, even when antivenom is injected only a few minutes after the accident. In this work, mice weighing 18-20 g (n = 5) were inoculated with 70 micrograms Bothrops jararacussu venom in 0.1 ml PBS in the gastrocnemius muscle. Mice were sacrificed using ether after 1, 12 hours, 3, 5, 7 days and 2, 3, 5, 6 weeks after the injection of the venom to obtain gastrocnemius muscles. They were fixed with Bouin's solution and stained using Hematoxylin--Eosin and Mason's trichromic stain was applied to visualize collagen fibers. Results showed that inflammatory reaction was evident after a few minutes of the venom injection, which was not evident after 6 weeks. Muscular fiber necrosis reached its highest level on the seventh day. Even thought regeneration of muscular fibers was important, they never reached the size of the control. We conclude that Bothrops jararacussu venom causes severe necrosis on muscle fibers with partial recovery, showing low hemorrhage and abundance of granulation tissue. This points that not all fibers were regenerated, which can be seen as a functional sequel for injured muscle.
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PMID:Muscular regeneration after myonecrosis induced by Bothrops jararacussu snake venom from Argentina. 1181 41

Surface properties of poly (D,L-lactide) (PDLLA) were modified by combining plasma treatment and collagen modification. The changes of surface properties were characterized by contact angles, surface energy, X-ray photoelectron spectra and scanning electron microscopy. The mouse 3T3 fibroblasts were used as model cells to evaluate the cell affinity of PDLLA before and after modification. Effects of different modification methods including plasma treatment, collagen coating and combining plasma treatment with collagen anchorage were investigated and compared. The results showed that the hydrophilicity and surface-free energy were improved and reduced, respectively, after each modification. Plasma pre-treatment could improve the roughness as it incorporated the polar groups and positively charged groups onto the sample surface; so the plasma pre-treated surface would benefit in anchoring more collagen tightly. As a result, cell affinity of PDLLA modified by combining plasma treatment with collagen anchorage was greatly improved. The modified materials could endure rinsing by PBS, which would facilitate further application when the modified materials were used as cells scaffold in tissue engineering.
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PMID:Enhanced cell affinity of poly (D,L-lactide) by combining plasma treatment with collagen anchorage. 1203 10

In subjects insufficiently controlled with low to moderate doses of inhaled corticosteroids, adding beta-agonists is clinically more beneficial than increasing the dose of inhaled corticosteroids. In the present study, we investigated the effect of adding salmeterol to fluticasone on allergen-induced airway inflammation and remodeling. Sensitized rats, in which characteristics of remodeling had been induced by ovalbumin exposure every 2 days from Days 14 to 28, were further exposed to ovalbumin or PBS from Days 29 to 42. During the last 2 weeks, before allergen exposure, rats were treated with aerosolized fluticasone propionate (10 mg), salmeterol (1 mg), salmeterol (1 mg) plus fluticasone propionate (10 mg), or placebo. After 4 weeks of ovalbumin exposure, the airways showed inflammatory changes, goblet cell hyperplasia, and enhanced fibronectin and collagen deposition. Salmeterol in monotherapy decreased bronchoalveolar lavage fluid eosinophil number but had no influence on structural changes. Combining salmeterol with fluticasone propionate counteracted goblet cell hyperplasia, but increased the amount of fibronectin and collagen in the airway wall. These effects of salmeterol did not influence airway responsiveness. We conclude that the combination of salmeterol and fluticasone propionate enhances aspects of allergen-induced airway remodeling. This is not accompanied by changes in airway responsiveness.
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PMID:Effect of combining salmeterol and fluticasone on the progression of airway remodeling. 1237 59

Cardiovascular diseases, such as atherosclerosis and hypertension, are associated with arterial stiffening. Previous studies showed that ANG II exacerbated atherosclerosis and induced hypertension and aneurysm formation in apolipoprotein E-deficient (apoE-KO) mice. The aim of the present study was to examine the effects of chronic treatment of ANG II on the arterial elastic properties in apoE-KO mice. We hypothesized that ANG II will injure the arterial wall resulting in increased arterial stiffening. Male apoE-KO mice were infused with either ANG II (1.44 mg. kg(-1). day(-1)) or vehicle (PBS) for 30 days. ANG II treatment accelerated atherosclerosis in the carotid artery by sixfold (P < 0.001) and increased blood pressure by 30% (P < 0.05). Additionally, our data demonstrated that ANG II increased arterial stiffening using both in vivo and in vitro methods. ANG II significantly increased pulse wave velocity by 36% (P < 0.01) and decreased arterial elasticity as demonstrated by a more than 900% increase in maximal stiffening (high strain Young's modulus) compared with vehicle (P < 0.05). These functional changes were correlated with morphological and biochemical changes as demonstrated by an increase in collagen content (60%), a decrease in elastin content (74%), and breaks in the internal elastic lamina in the aortic wall. In addition, endothelium-independent vasorelaxation to sodium nitroprusside was impaired in the aortic rings of ANG II-treated mice compared with vehicle. Thus, the present data indicate that ANG II injures the artery wall in multiple ways and arterial stiffening may be a common outcome of ANG II-induced arterial damage.
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PMID:Angiotensin II injures the arterial wall causing increased aortic stiffening in apolipoprotein E-deficient mice. 1238 74

IL-18 is an important cytokine in autoimmune and inflammatory diseases through the induction of IFN-gamma, TNF-alpha, and IL-1. We report herein that collagen-induced arthritis (CIA) in mice is inhibited by treatment with murine IL-18 binding protein (mIL-18BP). CIA was induced in DBA/1J mice by the injection of bovine type II collagen (CII) in IFA with added Mycobacterium tuberculosis on days 0 and 21. The mice were then treated for 3 wk with PBS or with two doses of mIL-18BP (0.5 and 3 mg/kg) as a fusion protein with the Fc portion of murine IgG1. Both the clinical disease activity scores and the histological scores of joint damage were reduced 50% in mice treated with either dose of mIL-18BP. Proliferation of CII-stimulated spleen and lymph node cells as well as the change in serum levels of IgG1 and IgG2a Ab to collagen between days 21 and 42 were decreased in mice treated with mIL-18BP. The production of IFN-gamma, TNF-alpha, and IL-1beta in cultured spleen cells was reduced by in vivo treatment with low dose, but not high dose, mIL-18BP. FACS analysis showed a slight decrease in NK cells and an increase in CD4(+) T cells in spleens of mice treated with mIL-18BP. The steady state mRNA levels of IFN-gamma, TNF-alpha, and IL-1beta in isolated joints were all decreased in mice treated with both doses of mIL-18BP. The mechanisms of mIL-18BP inhibition of CIA include reductions in cell-mediated and humoral immunity to collagen as well as decreases in production of proinflammatory cytokines in the spleen and joints.
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PMID:Mechanisms of inhibition of collagen-induced arthritis by murine IL-18 binding protein. 1257 81

Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. Thymosin beta 4 has previously been found to promote dermal and corneal repair in normal rats. Here we report that thymosin beta 4 was also active in accelerating wound repair in full-thickness dermal wounds in both db/db diabetic and aged mice. We found that thymosin beta 4 in either phosphate-buffered saline or a hydrogel formulation is active in promoting dermal wound repair in normal rats. In diabetic mice, where healing is delayed, we found that wound contracture and collagen deposition were significantly increased in the mice treated with thymosin beta 4 in either phosphate buffered saline solution or a hydrogel formulation. No difference was observed in keratinocyte migration, with all of the diabetic animals showing almost complete coverage of the wound at 8 days. Wound healing in 26-month-old (aged) animals was significantly delayed. Thymosin beta 4 accelerated wound healing in these aged mice, with increases in keratinocyte migration, wound contracture, and collagen deposition. The hydrogel formulation generally showed similar wound healing activity with thymosin beta 4 in PBS. The actin-binding domain of thymosin beta 4 duplicated in a seven-amino acid synthetic peptide, LKKTETQ, was able to promote repair in the aged animals comparable to that observed with the parent molecule. These studies show that thymosin beta 4 is active for wound repair in models of impaired healing and may have efficacy in chronic wounds in humans.
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PMID:Thymosin beta 4 and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. 1258 23


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