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Liver myofibroblasts from hepatitis B related liver failure patients may regulate natural killer cell function via PGE2.

Zhang M, Wang F, Chong Y, Tai Q, Zhao Q, Zheng Y, Peng L, Lin S, Gao Z - J Transl Med (2014)

Bottom Line: Natural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury.The inhibitory effect of LMFs on NK cells correlated with their ability to produce prostaglandin (PG) E2.These data suggest that LMFs may protect against immune-mediated liver injury in hepatitis B related LF patients by inhibiting NK cell function via PGE2.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China. zm20051208@163.com.

ABSTRACT

Background: Natural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury. However, few studies have investigated the phenotypes and functions of NK cells involved in hepatitis B related liver failure (LF), and the precise mechanism underlying NK cell regulation is not fully understood.

Methods: We detected the percentage and function of peripheral NK cells both in hepatitis B related LF patients and healthy volunteers by flow cytometry and isolated the liver myofibroblasts (LMFs) from hepatitis B related LF livers. To determine the possible effects of LMFs on NK cells, mixed cell cultures were established in vitro.

Results: We found a down-regulated percentage of peripheral NK cells in hepatitis B related LF patients, and their NK cells also displayed decreased activated natural cytotoxicity receptors (NCRs) and cytokine production. In a co-culture model, LMFs sharply attenuated IL-2-induced NK cell triggering receptors, cytotoxicity, and cytokine production. The inhibitory effect of LMFs on NK cells correlated with their ability to produce prostaglandin (PG) E2.

Conclusion: These data suggest that LMFs may protect against immune-mediated liver injury in hepatitis B related LF patients by inhibiting NK cell function via PGE2.

No MeSH data available.


Related in: MedlinePlus

LMFs regulate NK cell function. NK cells were cultured in rhIL-2 alone or with the indicated fibroblast cells and analyzed by flow cytometry. (A) After 5 days of culture in the absence or presence of rhIL-2, the triggering receptors, cytolytic granules and cytokine production of NK cells were analyzed. (B) The expression of NK cell triggering receptors was analyzed. (C) Intracytoplasmic analysis of granzyme B and perforin expression. (D) Analysis of the production of IFN-γ and TNF-α by NK cells under different conditions. (E) LMF-conditioned NK cells showed reduced cytotoxicity against K562 cells at different T/E ratios. The mean fluorescence intensities (MFI; indicated as the mean ± SEM of 7 independent experiments; A, B and C) and the percentages of positive cells (D) or apoptotic cells (E) are shown. The open profiles with dotted lines show the isotype control, and the open profiles with solid lines show the expression of the indicated markers.
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Fig3: LMFs regulate NK cell function. NK cells were cultured in rhIL-2 alone or with the indicated fibroblast cells and analyzed by flow cytometry. (A) After 5 days of culture in the absence or presence of rhIL-2, the triggering receptors, cytolytic granules and cytokine production of NK cells were analyzed. (B) The expression of NK cell triggering receptors was analyzed. (C) Intracytoplasmic analysis of granzyme B and perforin expression. (D) Analysis of the production of IFN-γ and TNF-α by NK cells under different conditions. (E) LMF-conditioned NK cells showed reduced cytotoxicity against K562 cells at different T/E ratios. The mean fluorescence intensities (MFI; indicated as the mean ± SEM of 7 independent experiments; A, B and C) and the percentages of positive cells (D) or apoptotic cells (E) are shown. The open profiles with dotted lines show the isotype control, and the open profiles with solid lines show the expression of the indicated markers.

Mentions: We next sought to determine whether LMFs were able to regulate NK cell phenotypes and functions. NK cells freshly isolated from the circulation of healthy donors were cultured in the absence or presence of rhIL-2. After 5 days of culture, the expression of NK cell triggering receptors (including NKp46, NKp30, NKp44, NKG2D and DNAM-1) and the CD69 activation marker was significantly up-regulated in the presence of rhIL-2 (Figure 3A). In addition, the release of cytolytic granules (perforin and granzyme B) and the secretion of cytokines (TNF-α and IFN-γ) were up-regulated by rhIL-2 treatment (Figure 3A).Figure 3


Liver myofibroblasts from hepatitis B related liver failure patients may regulate natural killer cell function via PGE2.

Zhang M, Wang F, Chong Y, Tai Q, Zhao Q, Zheng Y, Peng L, Lin S, Gao Z - J Transl Med (2014)

LMFs regulate NK cell function. NK cells were cultured in rhIL-2 alone or with the indicated fibroblast cells and analyzed by flow cytometry. (A) After 5 days of culture in the absence or presence of rhIL-2, the triggering receptors, cytolytic granules and cytokine production of NK cells were analyzed. (B) The expression of NK cell triggering receptors was analyzed. (C) Intracytoplasmic analysis of granzyme B and perforin expression. (D) Analysis of the production of IFN-γ and TNF-α by NK cells under different conditions. (E) LMF-conditioned NK cells showed reduced cytotoxicity against K562 cells at different T/E ratios. The mean fluorescence intensities (MFI; indicated as the mean ± SEM of 7 independent experiments; A, B and C) and the percentages of positive cells (D) or apoptotic cells (E) are shown. The open profiles with dotted lines show the isotype control, and the open profiles with solid lines show the expression of the indicated markers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4232720&req=5

Fig3: LMFs regulate NK cell function. NK cells were cultured in rhIL-2 alone or with the indicated fibroblast cells and analyzed by flow cytometry. (A) After 5 days of culture in the absence or presence of rhIL-2, the triggering receptors, cytolytic granules and cytokine production of NK cells were analyzed. (B) The expression of NK cell triggering receptors was analyzed. (C) Intracytoplasmic analysis of granzyme B and perforin expression. (D) Analysis of the production of IFN-γ and TNF-α by NK cells under different conditions. (E) LMF-conditioned NK cells showed reduced cytotoxicity against K562 cells at different T/E ratios. The mean fluorescence intensities (MFI; indicated as the mean ± SEM of 7 independent experiments; A, B and C) and the percentages of positive cells (D) or apoptotic cells (E) are shown. The open profiles with dotted lines show the isotype control, and the open profiles with solid lines show the expression of the indicated markers.
Mentions: We next sought to determine whether LMFs were able to regulate NK cell phenotypes and functions. NK cells freshly isolated from the circulation of healthy donors were cultured in the absence or presence of rhIL-2. After 5 days of culture, the expression of NK cell triggering receptors (including NKp46, NKp30, NKp44, NKG2D and DNAM-1) and the CD69 activation marker was significantly up-regulated in the presence of rhIL-2 (Figure 3A). In addition, the release of cytolytic granules (perforin and granzyme B) and the secretion of cytokines (TNF-α and IFN-γ) were up-regulated by rhIL-2 treatment (Figure 3A).Figure 3

Bottom Line: Natural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury.The inhibitory effect of LMFs on NK cells correlated with their ability to produce prostaglandin (PG) E2.These data suggest that LMFs may protect against immune-mediated liver injury in hepatitis B related LF patients by inhibiting NK cell function via PGE2.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong Province, China. zm20051208@163.com.

ABSTRACT

Background: Natural killer (NK) cells are abundant in the liver and constitute a major innate immune component that contributes to immune-mediated liver injury. However, few studies have investigated the phenotypes and functions of NK cells involved in hepatitis B related liver failure (LF), and the precise mechanism underlying NK cell regulation is not fully understood.

Methods: We detected the percentage and function of peripheral NK cells both in hepatitis B related LF patients and healthy volunteers by flow cytometry and isolated the liver myofibroblasts (LMFs) from hepatitis B related LF livers. To determine the possible effects of LMFs on NK cells, mixed cell cultures were established in vitro.

Results: We found a down-regulated percentage of peripheral NK cells in hepatitis B related LF patients, and their NK cells also displayed decreased activated natural cytotoxicity receptors (NCRs) and cytokine production. In a co-culture model, LMFs sharply attenuated IL-2-induced NK cell triggering receptors, cytotoxicity, and cytokine production. The inhibitory effect of LMFs on NK cells correlated with their ability to produce prostaglandin (PG) E2.

Conclusion: These data suggest that LMFs may protect against immune-mediated liver injury in hepatitis B related LF patients by inhibiting NK cell function via PGE2.

No MeSH data available.


Related in: MedlinePlus