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

Acne is a human disease of the sebaceous hair follicle. Unlike humans, most animals produce little or no triglycerides in hair follicles to harbor Propionibacterium acnes a fact that has encumbered the development of novel treatments for acne lesions. Although genetic mutant mice with acne-like skins have been used for screening anti-acne drugs, the mice generally have deficits in immune system that turns out to be inappropriate to generate antibodies for developing acne vaccines. Here, we employed a bioengineering approach using a tissue chamber integrated with a dermis-based cell-trapped system (DBCTS) to mimic the in vivo microenvironment of acne lesions. Human sebocyte cell lines were grown in DBCTS as a scaffold and inserted into a perforated tissue chamber. After implantation of a tissue chamber bearing human sebocytes into ICR mice, P. acnes or PBS was injected into a tissue chamber to induce host immune response. Infiltrated cells such as neutrophils and macrophages were detectable in tissue chamber fluids. In addition, a proinflammatory cytokine macrophage-inflammatory protein-2 (MIP-2) was elevated after P. acnes injection. In tissue chamber fluids, 13 proteins including secreted proteins and cell matrix derived from mouse, human cells or P. acnes were identified by proteomics using isotope-coded protein label (ICPL) coupled to nano-LC-MS analysis. After P. acnes infection, four proteins including fibrinogen, alpha polypeptide, fibrinogen beta chain, S100A9, and serine protease inhibitor A3K showed altered concentrations in the mimicked acne microenvironment. The bioengineered acne model thus provides an in vivo microenvironment to study the interaction of host with P. acnes and offers a unique set-up for screening novel anti-acne drugs and vaccines.
 ...
PMID:Bioengineering a humanized acne microenvironment model: proteomics analysis of host responses to Propionibacterium acnes infection in vivo. 1865 8

The purpose of this study was to assess in rats the pharmacological parameters and effects on gene expression in the liver of the triterpene glycoside actein. Actein, an active component from the herb black cohosh, has been shown to inhibit the proliferation of human breast cancer cells. To conduct our assessment, we determined the molecular effects of actein on livers from Sprague-Dawley rats treated with actein at 35.7 mg/kg for 6 and 24 h. Chemogenomic analyses indicated that actein elicited stress and statin-associated responses in the liver; actein altered expression of cholesterol and fatty acid biosynthetic genes, p53 pathway genes, CCND1 and ID3. Real-time RT-PCR validated that actein induced three time-dependent patterns of gene expression in the liver: (i) a decrease followed by a significant increase of HMGCS1, HMGCR, HSD17B7, NQO1, S100A9; (ii) a progressive increase of BZRP and CYP7A1 and (iii) a significant increase followed by a decrease of CCND1 and ID3. Consistent with actein's statin- and stress-associated responses, actein reduced free fatty acid and cholesterol content in the liver by 0.6-fold at 24 h and inhibited the growth of human HepG2 liver cancer cells. To determine the bioavailability of actein, we collected serum samples for pharmacokinetic analysis at various times up to 24 h. The serum level of actein peaked at 2.4 microg/mL at 6 h. Actein's ability to alter pathways involved in lipid disorders and carcinogenesis may make it a new agent for preventing and treating these major disorders.
 ...
PMID:Actein activates stress- and statin-associated responses and is bioavailable in Sprague-Dawley rats. 1952

Calprotectin is a heterodimer of the proteins S100A8 and S100A9, and it is an abundant innate immune protein associated with inflammation. In humans, calprotectin transcription and protein abundance are associated with asthma and disease severity. However, mechanistic studies in experimental asthma models have been inconclusive, identifying both protective and pathogenic effects of calprotectin. To clarify the role of calprotectin in asthma, calprotectin-deficient S100A9-/- and wild-type (WT) C57BL/6 mice were compared in a murine model of allergic airway inflammation. Mice were intranasally challenged with extracts of the clinically relevant allergen, Alternaria alternata (Alt Ext), or PBS every third day over 9 days. On Day 10, BAL fluid and lung tissue homogenates were harvested and allergic airway inflammation was assessed. Alt Ext challenge induced release of S100A8/S100A9 to the alveolar space and increased protein expression in the alveolar epithelium of WT mice. Compared with WT mice, S100A9-/- mice displayed significantly enhanced allergic airway inflammation, including production of IL-13, CCL11, CCL24, serum IgE, eosinophil recruitment, and airway resistance and elastance. In response to Alt Ext, S100A9-/- mice accumulated significantly more IL-13+IL-5+CD4+ T-helper type 2 cells. S100A9-/- mice also accumulated a significantly lower proportion of CD4+ T regulatory (Treg) cells in the lung that had significantly lower expression of CD25. Calprotectin enhanced WT Treg cell suppressive activity in vitro. Therefore, this study identifies a role for the innate immune protein, S100A9, in protection from CD4+ T-helper type 2 cell hyperinflammation in response to Alt Ext. This protection is mediated, at least in part, by CD4+ Treg cell function.
 ...
PMID:The Innate Immune Protein S100A9 Protects from T-Helper Cell Type 2-mediated Allergic Airway Inflammation. 3104 3