Complex regulation of the wound healing process involves multiple interactions among stromal tissue cells, inflammatory cells, and the extracellular matrix. Low molecular weight hyaluronan (LMW HA) derived from the degradation of high molecular weight hyaluronan (HMW HA) is suggested to activate cells involved in wound healing through interaction with HA receptors. In particular, receptor CD44 is suggested to mediate cell response to HA of different MW, being the main cell surface HA receptor in stromal tissue and immune cells. However, the response of dermal fibroblasts, the key players in granulation tissue formation within the wound healing process, to LMW HA and their importance for the activation of immune cells is unclear. In this study we show that LMW HA (4.3kDa) induced pro-inflammatory cytokine IL-6 and chemokines IL-8, CXCL1, CXCL2, CXCL6 and CCL8 gene expression in normal human dermal fibroblasts (NHDF) that was further confirmed by increased levels of IL-6 and IL-8 in cell culture supernatants. Conversely, NHDF treated by HMW HA revealed a tendency to decrease the gene expression of these cytokine and chemokines when compared to untreated control. The blockage of CD44 expression by siRNA resulted in the attenuation of IL-6 and chemokines expression in LMW HA treated NHDF suggesting the involvement of CD44 in LMW HA mediated NHDF activation. The importance of pro-inflammatory mediators produced by LMW HA triggered NHDF was evaluated by significant activation of blood leukocytes exhibited as increased production of IL-6 and TNF-α. Conclusively, we demonstrated a pro-inflammatory response of dermal fibroblasts to LMW HA that was transferred to leukocytes indicating the significance of LMW HA in the inflammatory process development during the wound healing process.
- MeSH
- antigeny CD44 metabolismus MeSH
- chemokiny biosyntéza genetika MeSH
- fibroblasty účinky léků imunologie MeSH
- interleukin-6 biosyntéza genetika metabolismus MeSH
- interleukin-8 biosyntéza MeSH
- kyselina hyaluronová farmakologie MeSH
- leukocyty účinky léků metabolismus MeSH
- lidé MeSH
- malá interferující RNA metabolismus MeSH
- mediátory zánětu metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- molekulová hmotnost MeSH
- přirozená imunita účinky léků genetika MeSH
- signální transdukce účinky léků genetika MeSH
- škára cytologie MeSH
- TNF-alfa biosyntéza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The clinical course of tick-borne encephalitis (TBE), a disease caused by TBE virus, ranges from asymptomatic or mild influenza-like infection to severe debilitating encephalitis or encephalomyelitis. Despite the medical importance of this disease, some crucial steps in the development of encephalitis remain poorly understood. In particular, the basis of the disease severity is largely unknown. METHODS: TBE virus growth, neutralizing antibody response, key cytokine and chemokine mRNA production and changes in mRNA levels of cell surface markers of immunocompetent cells in brain were measured in mice with different susceptibilities to TBE virus infection. RESULTS: An animal model of TBE based on BALB/c-c-STS/A (CcS/Dem) recombinant congenic mouse strains showing different severities of the infection in relation to the host genetic background was developed. After subcutaneous inoculation of TBE virus, BALB/c mice showed medium susceptibility to the infection, STS mice were resistant, and CcS-11 mice were highly susceptible. The resistant STS mice showed lower and delayed viremia, lower virus production in the brain and low cytokine/chemokine mRNA production, but had a strong neutralizing antibody response. The most sensitive strain (CcS-11) failed in production of neutralizing antibodies, but exhibited strong cytokine/chemokine mRNA production in the brain. After intracerebral inoculation, all mouse strains were sensitive to the infection and had similar virus production in the brain, but STS mice survived significantly longer than CcS-11 mice. These two strains also differed in the expression of key cytokines/chemokines, particularly interferon gamma-induced protein 10 (IP-10/CXCL10) and monocyte chemotactic protein-1 (MCP-1/CCL2) in the brain. CONCLUSIONS: Our data indicate that the genetic control is an important factor influencing the clinical course of TBE. High neutralizing antibody response might be crucial for preventing host fatality, but high expression of various cytokines/chemokines during TBE can mediate immunopathology and be associated with more severe course of the infection and increased fatality.
- MeSH
- buněčná imunita imunologie MeSH
- centrální nervový systém patologie MeSH
- chemokiny biosyntéza MeSH
- cytokiny biosyntéza MeSH
- genotyp MeSH
- klíšťová encefalitida imunologie patologie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- membránové proteiny biosyntéza MeSH
- messenger RNA biosyntéza genetika MeSH
- mozek - chemie fyziologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- náchylnost k nemoci MeSH
- neutralizující protilátky biosyntéza MeSH
- odolnost vůči nemocem MeSH
- plakové testy MeSH
- protilátky virové biosyntéza genetika MeSH
- virová nálož MeSH
- viry klíšťové encefalitidy * MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The role of infection in autoimmunity is widely discussed. In this study we concentrated on relationship between HELICOBACTER PYLORI as a very important gastroduodenal pathogen and autoimmune thyroiditis (AT). Forty seven AT patients and 34 healthy controls were enrolled. They were split into: THP ( H.PYLORI positive patients, n=17), THN ( H.PYLORI negative patients, n=30), CP ( H.PYLORI positive controls, n=17) and CN groups ( H.PYLORI negative controls, n=17). By protein microarray we analysed production of 23 cytokines and chemokines prior and post stimulation with H.PYLORI lysate and its lipopolysaccharide (LPS). Reactivity to lysate as well as to bacterial LPS differed within groups. The lowest basal cytokine and chemokine production was observed in CN group but these subjects reacted significantly to specific stimulation by increasing IFN-gamma (in comparison with THP p=0.01 for LPS and p=0.004 for H.PYLORI lysate) and TGF-beta production (p=0.015 for LPS). In contrast, IL-10 and IL-5 were decreased in this group. In CP, THN and THP groups, we observed in general higher chemokine response. THP group increased proinflammatory IL-6 after specific stimulation as well (in comparison with CP p<0.0001 for LPS stimulation). We observed different "reactivity pattern" to H.PYLORI within groups with low basal cytokine and chemokine production in healthy H.PYLORI negative controls but with clear specific response in IFN-gamma and TGF-beta production in this group. Adequate immune reaction which is joined to appropriate immunoregulation leads to prevention of the chronic infection and on the other hand may prevent the development of "connected" diseases such as autoimmune. J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart.New York.
- MeSH
- autoimunitní tyreoiditida imunologie mikrobiologie MeSH
- chemokiny biosyntéza MeSH
- čipová analýza proteinů MeSH
- cytokiny biosyntéza MeSH
- dítě MeSH
- dospělí MeSH
- ELISA MeSH
- Helicobacter pylori imunologie MeSH
- infekce vyvolané Helicobacter pylori imunologie mikrobiologie MeSH
- kultivované buňky MeSH
- leukocyty mononukleární imunologie MeSH
- lidé MeSH
- mladiství MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
AIMS: Proinflammatory cytokines are thought to play an important role in various kidney graft diseases resulting in interstitial fibrosis and tubular atrophy frequently found in case biopsies. To explore the role of various cytokines and chemokines in the long-term graft outcome, the transcription patterns of their genes in kidney allograft biopsies were evaluated. METHODS: The real-time RT-PCR was used to identify intragraft mRNA expression of cytokines and chemokines in 74 kidney graft recipients and the results were correlated with histological and clinical parameters and long-term graft outcome. RESULTS: We observed up-regulated IL-10 (p < 0.001), TGF-beta1, IL-6, MCP-1, RANTES (p < 0.01) and TNF-alpha (p < 0.05) mRNA expression in patients with chronic allograft nephropathy (CAN) as compared to controls. There were positive correlations between the mRNA expression of IL-6 (p < 0.001), IL-10 (p < 0.01), TNF-alpha, MCP-1 (p < 0.05) and the proteinuria. The up-regulation of intrarenal MCP-1 in patients with CAN increased the risk for the graft failure within the next 42 months (OR 5.1, p < 0.05). Kaplan-Meier survival analysis revealed that proteinuria and higher intragraft expression of TGF-beta1 and MCP-1 predict a poor kidney graft outcome. CONCLUSION: Expression patterns of intrarenal proinflammatory genes might discriminate patients at a higher risk for the earlier allograft failure. 2007 S. Karger AG, Basel
- MeSH
- chemokiny biosyntéza genetika MeSH
- cytokiny biosyntéza genetika MeSH
- dospělí MeSH
- financování organizované MeSH
- ledviny metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- přežívání štěpu genetika MeSH
- regulace genové exprese fyziologie MeSH
- rejekce štěpu genetika metabolismus MeSH
- transplantace ledvin MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- autoprotilátky imunologie izolace a purifikace MeSH
- chemokiny biosyntéza MeSH
- citrulin analogy a deriváty biosyntéza imunologie MeSH
- cytokiny biosyntéza MeSH
- lidé MeSH
- MAP kinasový signální systém genetika imunologie MeSH
- monoklonální protilátky terapeutické užití MeSH
- myozitida etiologie imunologie MeSH
- peptidy a proteiny asociované s receptory TNF MeSH
- revmatoidní artritida etiologie imunologie metabolismus MeSH
- vitamin D sekrece terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- bakteriální infekce * imunologie MeSH
- biologické markery analýza MeSH
- buněčné linie imunologie mikrobiologie MeSH
- chemokiny biosyntéza imunologie izolace a purifikace MeSH
- cytokiny biosyntéza imunologie izolace a purifikace MeSH
- exprese genu imunologie MeSH
- Francisella tularensis * patogenita MeSH
- makrofágy imunologie mikrobiologie MeSH
- polymerázová řetězová reakce MeSH
- proteosyntéza * imunologie MeSH
- techniky in vitro MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- chemokiny biosyntéza genetika MeSH
- fibroblasty genetika virologie MeSH
- kultivované buňky genetika virologie MeSH
- kuřecí embryo MeSH
- onkogenní viry fyziologie MeSH
- transformace genetická MeSH
- virové proteiny analýza fyziologie MeSH
- virus Markovy nemoci genetika MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- techniky in vitro MeSH
