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pmc-enju-pas

bionlp-st-ge-2016-test-proteins

bionlp-st-ge-2016-uniprot

GO-BP

GO-MF

GO-CC

{"project":"GO-CC","denotations":[{"id":"T12573","span":{"begin":3313,"end":3317},"obj":"http://purl.obolibrary.org/obo/GO_0005623"}],"text":"We confirmed and extended previous results [13-16] indicating that, in the absence of other stimuli, β-1→3-D-glucans induced binding of NFκB-, NFIL-6- and NFAT-mers to cytokine promoters. Because of the multiple band shifts observed for NFAT binding (Fig. 1A), one could speculate that there is activation of several different NFAT isoforms, probably derived from alternative splicing [38]. Interestingly, the GP-induced transcription factor binding transformed only into a very limited cytokine response, namely IL-8 and IL-1RA (Fig. 3B). Hence, our data are in aggreement with the few reports describing a β-1→3-D-glucan-mediated IL-8 [6,16,19] and IL-1RA production [17]. In addition, our EMSA/supershift and immunoblotting results demonstrated a GP-mediated predominant binding of NFκB p65 and to a lesser extent of p50 to a κB consensus site of the IL-8 promoter (Figs. 1A, 2). Results by Schulte and colleagues [28] pointed to an induction of IL-8 transcription depending on activation via an NFκB p65/65 homodimer, rather than via p65/50 heterodimers, which might be the case for the GP-mediated IL-8 transcription. A GP-mediated IL-8 transcription based upon a cooperation between transactivated NFκB p65 and NFIL-6 [13,39] or NFATc2 dimer binding to the IL-8κB site [38] seems also possible. The IL-8κB consensus site exhibits a preferentially p65 binding half site and thus differs from the κB half site described for TNFα and IL-1β [27,40], supporting the idea of regulating NFκB binding through combinatorial associations of the subunits and the specific sequence of the decameric κB motif [41,42]. Unlike LPS or TSST-1, we found that GP did not induce IL-1β, but it strongly induced IL-1RA, suggesting an immediate anti-inflammatory potential of GP. Analysing the IL-1RA promoter [34], we discovered four new binding sites (Fig. 8): an NFκB3 site (between -100 and -130), an NFκB consensus site (-266 and -280), another NFκB2/3 site (-288 and -302) and a more distal NFATP2/3 site (-471 and -490). Our data indicated that GP leads to production of IL-1RA primarily via induction of NFATP2/3 and NFIL-6 DNA binding, which might be due to differences in the binding motif or the composition of the activated transcription factors (NFAT) between the IFNγ, IL-6 and IL-1RA promoter. The differential decrease of NFκB, NFAT and NFIL-6 binding to sites in the IL-1RA promoter as well as of IL-1RA mRNA and protein induced by selective inhibitors prior to GP treatment might suggest that these steps are linked to each other and necessary for induction of IL-1RA (Fig. 7). Regarding cellular sources, both, monocytes as well as neutrophils have been reported to produce IL-1RA [32]. Flow cytometric experiments seemed to confirm that monocytes and neutrophils were able to produce IL-8 just as IL-1RA in response to GP (data not shown). This GP-induced cytokine profile was substantially more restricted than that of LPS or TSST-1, which is likely due to differences in recognition and signaling between LPS, TSST-1 and GP. Recognition of LPS is mainly mediated through Toll-like receptor 4 and subsequent signaling via the NFκB pathway, leading to expression of pro-inflammatory mediators like TNFα [43]. A bacterial superantigen like TSST-1 acts through binding to MHC-II molecules and subsequently the T cell receptor, leading to release of mainly IFNγ and TNFα, the latter via both, PI3K and p38 mitogen-activated kinase signaling [44,45]. Altogether, the induction of the neutrophil-attracting IL-8 and the anti-inflammatory IL-1RA by fungal carbohydrates (GP) may well fit to a benign PAMP response, mounting defensive mechanisms against a possible microbial attack."}

sentences

simple1

BioNLP16_DUT

BioNLP16_Messiy

DLUT931

bionlp-st-ge-2016-test-ihmc

bionlp-st-ge-2016-spacy-parsed

bionlp-st-ge-2016-test-tees

testone

test3

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PMC:1472690 / 24146-27824 JSON TXT