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Xu J  Chakrabarti AK  Tan JL  Ge L  Gambotto A  Vujanovic NL 《Blood》2007,109(8):3333-3341
Dendritic cells (DCs) and natural killer (NK) cells are essential components of the innate immune system and have a central role in initiation and regulation of adaptive immune responses. During the early critical immune activities, DCs and NK cells interact and reciprocally regulate each other via cell-cell contact. The molecular mediators of the DC-NK-cell crosstalk are largely undefined. In the present study, we show in mice that DC stimulation of NK-cell IFN-gamma secretion requires DC membrane-bound but not secreted products; is increased by augmenting the expression of DC transmembrane tumor necrosis factor (tmTNF) and NK-cell transmembrane TNF receptor type 2 (tmTNFR2); is inhibited by blocking TNF or TNFR2 but not TNFR1; is impaired by knocking out DC Tnf or NK-cell Tnfr2 but not DC Tnfr1 or Tnfr2 and NK-cell Tnf or Tnfr1; and is restored in TNF-deficient DCs by reconstituting tmTNF, but cannot be mimicked by soluble TNF. We also demonstrate that DC TNF and NK-cell TNFR2 are required for DC-mediated NK-cell proliferation and amplification of cytotoxic activity. These novel findings provide the first evidence that DC-NK-cell crosstalk mediates enhancement of NK-cell functions via triggering NK-cell tmTNFR2 by DC tmTNF.  相似文献   
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Human natural leukocytic interferon (HNLI) and recombinant interferon (rIFN) alpha 2c can be used in the therapy of basal cell carcinoma. Seventy-two patients were treated for 3 to 6 weeks with a single dose of 400,000 to 1,200,000 units (HNLI) and 2,000,000 to 5,000,000 units (rIFN alpha 2c). According to histopathologic and clinical findings, 52 patients were cured, and cancer cells were not found in the biopsy material taken after HNLI treatment for the second biopsy. In nine of 72 patients the cancer lesion was reduced 25% to 90%. In 11 patients it was not reduced or was reduced less than 25%. With rIFN alpha 2c therapy given five times per week for 4 weeks, histopathologic and clinical findings showed that five patients out of 12 were cured, and cancer cells were not found in the biopsy material taken after treatment. In seven patients out of 12 the cancer lesion was reduced 25% to 90%. Both types of interferons are effective in the treatment of basal cell carcinoma. Side effects were mild.  相似文献   
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Purpose: Adipose tissue expansion can occur through several different ways and, under certain conditions, can be connected with chronic inflammation. TNF-α is one of the important cytokines involved in this process. Prolonged inflammation in obesity can lead to obesity-related insulin resistance and tissue dysfunction. The aim of our study was to investigate how different combination of maternal and postnatal diet affects offspring adipose tissue morphology and adipose tissue TNF-α expression.

Methods: Ten female Sprague Dawley rats, 9 weeks old, were randomly divided into two groups and fed either standard laboratory chow or food rich in saturated fatty acids during 6 weeks and then mated with the same male rat. After birth and lactation male rat offspring from both groups were divided into four subgroups depending on the diet they were fed until 22 weeks old. Samples of white adipose tissue were taken from the subcutaneous, epididymal, and perirenal fat pad. On tissue sections, histomorphometric analysis was conducted using CellProfiler program v 2.1.1, and immunohistochemical staining for TNF-α was performed.

Results: Greater mean surface area of subcutaneous and epididymal adipocytes was found in groups of male rat offspring with altered diet. In perirenal adipose tissue, the highest number of adipocytes was measured in the group where both mother and offspring were fed a high-fat diet. Adipocyte staining intensity for TNF-α did not differ significantly between the groups.

Conclusions: Together with our previously published data, our results lead to the conclusion that alteration of postnatal diet can lead to TNF-α and adipocyte morphology changes.  相似文献   

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