RESUMO
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RESUMO
HSP47 is required for the production of collagen and serves an important role in tissue remodeling, a pathophysiologic mechanism of chronic rhinosinusitis (CRS). We investigated the relationship between HSP47 expression and tissue remodeling in CRS. We also determined the underlying molecular mechanisms of TGF-ß1-induced HSP47 and extracellular matrix (ECM) production in nasal fibroblasts. HSP47, α-SMA, fibronectin, and collagen type I expression levels were measured using real-time PCR, western blotting, and immunofluorescence staining. Fibroblast migration was analyzed using scratch and transwell migration assays. Contractile activity was measured with a collagen gel contraction assay. HSP47 is increased in patients with CRS without nasal polyps. TGF-ß1 induced HSP47 expression in nasal fibroblasts. Myofibroblast differentiation and ECM production, which are induced by TGF-ß1, were inhibited by siHSP47. We also confirmed that the Smad2/3 signaling pathway is involved in TGF-ß1-induced HSP47 expression in nasal fibroblasts. In a functional assay, TGF-ß1-enhanced migration and contraction ability were inhibited by HSP47 knockout. Glucocorticoid reversed the stimulatory effects of TGF-ß1 on HSP47 expression and ECM production in nasal fibroblasts and ex vivo organ cultures. HSP47 expression is involved in TGF-ß1-induced myofibroblast differentiation and ECM production through the Smad2/3 signaling pathway, which might contribute to tissue remodeling in chronic rhinosinusitis.
Assuntos
Proteínas de Choque Térmico HSP47/genética , Pólipos Nasais/genética , Rinite/genética , Sinusite/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Colágeno/biossíntese , Matriz Extracelular , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia , Proteína Smad2/genética , Proteína Smad3/genéticaRESUMO
Resistance to antimicrobials was measured in 73 isolates of Campylobacter jejuni (C. jejuni) and 121 isolates of Campylobacter coli (C. coli) from chicken and swine feces and carcasses in Korea. Both bacterial species showed the highest resistance to (fluoro) quinolones (ciprofloxacin and nalidixic acid) out of the nine antimicrobials tested. Erythromycin resistance was much higher in C. coli (19.0%, 23/121) than in C. jejuni (6.8%, 5/73). The mutation in the 23S rRNA gene was primarily responsible for macrolide resistance in Campylobacter isolates. Several amino acid substitutions in the L4 and L22 ribosomal proteins may play a role in the mechanism of resistance, but the role requires further evaluation. A total of eight virulence genes were detected in 28 erythromycin-resistant Campylobacter isolates. All C. jejuni isolates carried more than four such genes, while C. coli isolates carried fewer than three such genes. The high rate of resistance highlights the need to employ more prudent use of critically important antimicrobials, such as fluoroquinolones and macrolides, in swine and poultry production, and to more carefully monitor antimicrobial resistance in Campylobacter isolates in food animals.
Assuntos
Antibacterianos/farmacologia , Campylobacter coli/efeitos dos fármacos , Campylobacter jejuni/efeitos dos fármacos , Galinhas/microbiologia , Eritromicina/farmacologia , Fezes/microbiologia , Macrolídeos/farmacologia , Carne/microbiologia , Suínos/microbiologia , Fatores de Virulência/genética , Animais , Campylobacter coli/genética , Campylobacter coli/isolamento & purificação , Campylobacter jejuni/genética , Campylobacter jejuni/isolamento & purificação , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Mutação Puntual , RNA Ribossômico 23S/genética , República da CoreiaRESUMO
This study was conducted to examine the in vitro activity of antimicrobials against Campylobacter spp. isolates from chicken and human sources and the genetic interrelation among them. During 2004-2008, a total of 173 Campylobacter spp. isolated from chicken meats (60 domestic and 62 imported chicken meats) and humans (n = 51) were tested for susceptibility to nine antimicrobials. Of 173 isolates, 140 (80.9%) showed multidrug resistance (MDR) against three to eight antimicrobials. The most frequent pattern type was MDR to four antimicrobials: ciprofloxacin, nalidixic acid, ampicillin, and tetracycline. Over 52.6% (91/173) of the isolates tested were resistant to these four antibiotics simultaneously. Especially, two and five isolates originated from Korea and Brazil showed resistance against all antibiotics tested, except for florfenicol. Further, 95% (57/60) of the isolates originated from domestic chicken showed resistance to ciprofloxacin, the antimicrobial agent of choice for treatment of human campylobacteriosis. Genotypic characterization of all Campylobacter isolates performed by pulsed-field gel electrophoresis yielded 74 types among the 173 isolates. Isolates sharing the same or similar genetic clusters were detected in different countries at different times. The pulsed-field gel electrophoresis patterns of chicken-related isolates were closely related to those of isolates from humans with gastroenteritidis. The results of this study suggest that MDR Campylobacter spp. are widespread and that Campylobacter with similar genotypes are circulating both in humans and in chicken meat in Korea.
Assuntos
Antibacterianos/farmacologia , Infecções por Campylobacter/microbiologia , Campylobacter/efeitos dos fármacos , Campylobacter/genética , Carne/microbiologia , Animais , Brasil , Campylobacter/classificação , Campylobacter/isolamento & purificação , Galinhas , DNA Bacteriano/química , Farmacorresistência Bacteriana Múltipla , Eletroforese em Gel de Campo Pulsado , Europa (Continente) , Contaminação de Alimentos/análise , Genótipo , Humanos , Testes de Sensibilidade Microbiana , República da Coreia , Tailândia , Estados UnidosRESUMO
Campylobacteriosis in humans is primarily caused by handling or consuming contaminated poultry or their products. The aims of this study were to estimate the prevalence of Campylobacter spp. in domestic and imported poultry meat in Korea and to further characterize the obtained isolates. From 2004 to 2008, a total of 475 domestic and 867 imported raw poultry meat samples were examined for the presence of Campylobacter spp. Among 475 domestic poultry meat samples, Campylobacter jejuni and Campylobacter coli were isolated from 219 (46.1%) and 156 (32.8%), respectively. Relative prevalence of C. jejuni and C. coli was higher in meat from Brazil (39/78, 50.0% and 7/78, 8.9%) and France (32/96, 33.3% and 8/96, 8.3%), whereas lower in meat from Denmark (72/516, 14.0% and 12/516, 2.3%) and Thailand (5/39, 12.8% and 3/39, 7.6%). The resistance to ampicillin and tetracycline was highly prevalent in Campylobacter spp. from most countries investigated, whereas lower in meat from Denmark. On the other hand, the prevalence of erythromycin and gentamicin resistance was less than 10% in most countries. The resistance rate to nalidixic acid, ciprofloxacin, and enrofloxacin ranged from 11.9% to 87.5%. The use of fla-polymerase chain reactionrestriction fragment length polymorphism for epidemiological analysis found that some pattern types were considerably more frequent and distinct in meat from each country. In conclusion, we report the presence of high contamination in domestic and imported poultry meat in Korea and the antimicrobial and genetic diversity of Campylobacter spp. between each country.