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Immune response against HtrA proteases in children with cutaneous mastocytosis

100%
Renke J., Kędzierska-Mieszkowska S., Lange M., Nedoszytko B., Liberek A., Plata-Nazar K., Renke M., Wenta T., Żurawa-Janicka D., Skórko-Glonek J., Lipińska B.
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2018
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vol. 65
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issue 3
471-478
EN
Mast cells play an important role in both, the innate and adaptive immunity, however, clonal proliferation of abnormal mast cells in various organs leads to mastocytosis. A skin variant of the disease, cutaneous mastocytosis (CM) is the most frequent form of mastocytosis in children. HtrA proteases are modulators of important cellular processes, including cell signaling and apoptosis, and are related to development of several pathologies. The above and the observation that mast cells constitutively release the HtrA1 protein, prompted us to investigate a possible involvement of the HtrA proteins in pediatric CM. Levels of the serum autoantibodies (IgG) against the recombinant HtrA proteins (HtrA1-4) in children with CM (n=36) and in healthy controls (n=62) were assayed. Anti-HtrA IgGs were detected using enzyme linked immunosorbent assay (ELISA) and Western-blotting. In the CM sera, levels of the anti-HtrA1 and anti-HtrA3 autoantibodies were significantly increased when compared to the control group, while the HtrA protein levels were comparable. No significant differences in the anti-HtrA2 IgG level were found; for the anti-HtrA4 IgGs lower levels in CM group were revealed. In healthy children, the IgG levels against the HtrA1, -3 and -4 increased significantly with the age of children; no significant changes were observed for the anti-HtrA2 IgG. Our results suggest involvement of the HtrA1 and HtrA3 proteins in pediatric CM; involvement of the HtrA4 protein is possible but needs to be investigated further. In healthy children, the autoantibody levels against HtrA1, -3 and -4, but not against HtrA2, increase with age.
2
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Interstitial Cajal-Like Cells and Bile Lithogenicity in the Pathogenesis of Gall-Stone Disease

88%
Pasternak A., Matyja A., Gil K., Gajda M., Tomaszewski K. A., Matyja M., Walocha J. A., Kulig J.
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vol. 85
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issue 6
311-316
EN
Gall-stone disease constitutes a serious clinical problem and is the most frequent cause of elective cholecystectomies. There are many etiopatogenic factors however; lithogenic bile and its stasis due to gall-bladder hypomotility seem to be the most important. In recent years discovery of pacemaker function of Interstitial Cells of Cajal changed our understanding of smooth muscle physiology and helped to disclose many gastrointestinal motility disorders. The aim of the study was identification and quantification of interstitial Cajal-like cells (ICLCs) in gall-bladder muscle wall from patients with cholelithiasis and in gall-stone-free controls, as well as determination of the relationship between the number of ICLCs and Cholesterol Saturation Index (CSI) of bile in both analyzed groups. Material and methods. 20 patients operated for symptomatic cholelithiasis were enrolled into the study group. The control group consisted of 20 patients operated for pancreatic head tumors, with no pre- and intraoperative signs of gall-stones. Identification of ICLCs in the gall-bladder was performed by means of double immunofluorescence technique with anti c-Kit and anti-mast cell tryptase antibodies. Quantitative analysis was carried out under fluorescence microscopy conjoined with image analysis software. Bile samples were used for calculation of CSI. Results. ICLCs were detected within gall-bladder muscle wall. Number of ICLCs was statistically significantly lower in patients from the study group as compared to control. The study also revealed statistically significantly higher CSI in the study group. Conclusions. The quantity of ICLCs is diminished in the gall-bladder from patients with cholelithiasis and there is negative correlation between the number of ICLCs and CSI of bile. Regarding the role of ICCs in regulation of GI tract motility, it appears that reduction in their number may be important etiopatogenic factor of cholelithiasis.
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Irisflorentin suppresses allergic inflammation in mast cells via reducing histamine release and production of pro-inflammatory cytokines

88%
Li Y., Meng F.
Acta Poloniae Pharmaceutica - Drug Research
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2019
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vol. 76
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issue 4
725-733
EN
Allergic diseases afflict many people worldwide. Allergic inflammation encompassing acute allergic reaction and chronic inflammatory response is the major pathogenesis. To discovery novel therapeutic approach for allergic diseases, we have evaluated the anti-allergic inflammatory effects of irisflorentin using RBL-2H3 cells. The results showed certain concentrations of irisflorentin could suppress histamine release and secretion of TNF-α, IL-1β and IL-6. Further investigations indicated that the effects of irisflorentin were associated with a reduction of intracellular calcium, suppression of NF-κB signaling pathway and inhibition of caspase-1 activity. Therefore, the results of the current study demonstrated that irisflorentin can ameliorate mast cell-mediated allergic inflammation. These results can provide evidences for the discovery of novel therapy for allergic diseases and application of irisflorentin in practice.
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