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- Silverpil, Elin, 1978, et al.
(författare)
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Negative feedback on IL-23 exerted by IL-17A during pulmonary inflammation
- 2013
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 19:5, s. 479-492
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Tidskriftsartikel (refereegranskat)abstract
- It is now established that IL-17 has a broad pro-inflammatory potential in mammalian host defense, in inflammatory disease and in autoimmunity, whereas little is known about its anti-inflammatory potential and inhibitory feedback mechanisms. Here, we examined whether IL-17A can inhibit the extracellular release of IL-23 protein, the upstream regulator of IL-17A producing lymphocyte subsets, that is released from macrophages during pulmonary inflammation. We characterized the effect of IL-17A on IL-23 release in several models of pulmonary inflammation, evaluated the presence of IL-17 receptor A (RA) and C (RC) on human alveolar macrophages and assessed the role of the Rho family GTPase Rac1 as a mediator of the effect of IL-17A on the release of IL-23 protein. In a model of sepsis-induced pneumonia, intravenous exposure to Staphylococcus aureus caused higher IL-23 protein concentrations in cell-free bronchoalveolar lavage (BAL) samples from IL-17A knockout (KO) mice, compared with wild type (WT) control mice. In a model of Gram-negative airway infection, pre-treatment with a neutralizing anti-IL-17A Ab and subsequent intranasal (i.n.) exposure to LPS caused higher IL-23 and IL-17A protein concentrations in BAL samples compared with mice exposed to LPS, but pre-treated with an isotype control Ab. Moreover, i.n. exposure with IL-17A protein per se decreased IL- 23 protein concentrations in BAL samples. We detected IL-17RA and IL-17RC on human alveolar macrophages, and found that invitro stimulation of these cells with IL-17A protein, after exposure to LPS, decreased IL-23 protein in conditioned medium, but not IL-23 p19 or p40 mRNA. This study indicates that IL-17A can partially inhibit the release of IL-23 protein during pulmonary inflammation, presumably by stimulating the here demonstrated receptor units IL-17RA and IL-17RC on alveolar macrophages. Hypothetically, the demonstrated mechanism may serve as negative feedback to protect from excessive IL-17A signaling and to control antibacterial host defense once it is activated.
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- Ostadkarampour, M., et al.
(författare)
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Higher levels of interleukin IL-17 and antigen-specific IL-17 responses in pulmonary sarcoidosis patients with Lofgren's syndrome
- 2014
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 178:2, s. 342-352
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Tidskriftsartikel (refereegranskat)abstract
- Sarcoidosis is a granulomatous disorder of unknown aetiology. The presence of Mycobacterium tuberculosis catalase-peroxidase (mKatG) in sarcoidosis tissue has been reported. T helper type 1 (Th1) responses against mKatG have previously been observed. However, little is known about interleukin (IL)-17 and Th17 responses in sarcoidosis. Here, we investigated the levels of IL-17 and frequencies of IL-17-producing cells responding to mKatG in sarcoidosis patients with different prognosis. Peripheral blood and bronchoalveolar lavage (BAL) cells were obtained from sarcoidosis patients with or without Lofgren's syndrome (often associated with spontaneous recovery), and also stratified according to human leucocyte antigen (HLA) type. Cells producing IL-17 and interferon (IFN)-gamma after stimulation with mKatG were enumerated by enzyme-linked immunospot (ELISPOT). The level of IL-17 in the BAL fluid of sarcoidosis patients and healthy controls was measured by quantitative immuno-polymerase chain reaction (qIPCR). We also performed flow cytometry and immunohistochemistry for further characterization of IL-17 expression. Patients with Lofgren's syndrome had a higher frequency of IL-17-producing cells responding to mKatG in BAL fluid compared to patients without Lofgren's syndrome (P < 0.05). The HLA-DR3(+) sarcoidosis patients with Lfgren's syndrome (known to have a particularly good prognosis) also had a clearly higher level of IL-17 in BAL fluid compared to healthy controls and sarcoidosis patients without Lofgren's syndrome (P < 0.01) and (P < 0.05), respectively. No such difference between patient groups was observed with regard to IFN-gamma and not with regard to either cytokine in peripheral blood. These findings suggest that IL-17-producing cells may be a useful biomarker for the prognosis of sarcoidosis and play a role in the spontaneous recovery typical of patients with Lfgren's syndrome.
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- Abuzeid, Nadir, et al.
(författare)
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Antimycobacterial activity of selected medicinal plants traditionally used in Sudan to treat infectious diseases
- 2014
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Ingår i: Journal of Ethnopharmacology. - : Elsevier. - 0378-8741 .- 1872-7573. ; 157, s. 134-139
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Tidskriftsartikel (refereegranskat)abstract
- Ethnopharmacological relevance: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis underscores the need for continuous development of new and efficient methods to determine the susceptibility of isolates of Mycobacterium tuberculosis in the search for novel antimycobacterial agents. Natural products constitute an important source of new drugs, and design and implementation of antimycobacterial susceptibility testing methods are necessary to evaluate the different extracts and compounds. In this study we have explored the antimycobacterial properties of 50 ethanolic extracts from different parts of 46 selected medicinal plants traditionally used in Sudan to treat infectious diseases. Materials and methods: Plants were harvested and ethanolic extracts were prepared. For selected extracts, fractionation with hydrophilic and hydrophobic solvents was undertaken. A luminometry-based assay was used for determination of mycobacterial growth in broth cultures and inside primary human macrophages in the presence or absence of plant extracts and fractions of extracts. Cytotoxicity was also assessed for active fractions of plant extracts. Results: Of the tested extracts, three exhibited a significant inhibitory effect on an avirulent strain of Mycobacterium tubercluosis (H37Ra) at the initial screening doses (125 and 6.25 mu g/ml). These were bark and leaf extracts of Khaya senegalensis and the leaf extract of Rosmarinus officinalis L. Further fractions of these plant extracts were prepared with n-hexane, chloroform, ethyl acetate, n-butanol, ethanol and water, and the activity of these extracts was retained in hydrophobic fractions. Cytotoxicity assays revealed that the chloroform fraction of Khaya senegalensis bark was non-toxic to human monocyte-derived macrophages and other cell types at the concentrations used and hence, further analysis, including assessment of IC50 and intracellular activity was done with this fraction. Conclusion: These results encourage further investigations to identify the active compound(s) within the chloroform fraction of Khaya senegalensis bark. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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- Glader, A, et al.
(författare)
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Byggnadsrelaterad ohälsa : Kompetensutveckling inom hälsovården
- 2014
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Rapport (refereegranskat)abstract
- Det finns ett stort behov av utbildning om inomhusmiljö och byggnadsrelaterad ohälsa, både inom ramen för grundläggande yrkesutbildningar och som fortbildningskurser för yrkesverksamma. Hälsoproblem som beror på dålig inomhusluft på arbetsplatsen utreds av företagshälsovården. Dock har de som jobbar inom företagshälsovård idag inte alltid tillräcklig kunskap om inomhusmiljö och byggnadsrelaterad ohälsa och saknar ofta beredskap att som sakkunniga delta i utredningar på arbetsplatser. För att förbättra vården bör personalen utbildas om bl.a. riskfaktorer för dålig inomhusluft, vanliga hälsobesvär och inverkan på arbetsförmåga och produktivitet, de psykosociala faktorernas betydelse samt ansvarsfrågor och hälsoekonomiska konsekvenser. Öppna digitala lärresurser (OER) och kurser på nätet (MOOCs) kan med fördel användas vid fortbildning av vårdpersonal. Nätbaserad utbildning underlättar för vårdpersonalen att själv kunna välja tidpunkt och målsättning. Därtill utgör OER även ett hjälpmedel för att utveckla kunskapsöverföringen mellan Sverige och Finland.
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- Glader, C A, et al.
(författare)
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Lipoprotein(a), Chlamydia pneumoniae, leptin and tissue plasminogen activator as risk markers for valvular aortic stenosis.
- 2003
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Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 24:2, s. 198-208
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The aim of the present study was to identify risk markers for the development of valvular aortic stenosis (AS). Lipoprotein(a) (Lp(a)) and Chlamydia pneumoniae IgG antibody titres in plasma and in circulating immune complexes as well as leptin and tissue plasminogen activator (t-PA) in plasma were studied.METHODS AND RESULTS: One hundred and one patients (41 women and 60 men, mean age 71+/-8 years) with significant AS and 101 age- and sex-matched controls were included in this study. All patients underwent aortic valve replacement at the University Hospital in Umeå, Sweden. The controls had no symptoms of cardiovascular disease and they were examined echocardiographically. An Lp(a) level >or=480 mg x l(-1), a C. pneumoniae-specific IgG titre >or=1/128, a high leptin level and a high t-PA mass concentration in plasma were identified as risk markers for AS. A strong synergism between Lp(a) and C. pneumoniae IgG antibodies in circulating immune complexes was found.CONCLUSION: Our data indicate that a chronic C. pneumoniae infection and a high plasma Lp(a) level might influence and aggravate aortic heart valve sclerosis via the formation of circulating immune complexes. The present study also strongly suggests an association between high plasma leptin, t-PA mass concentration and AS.
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