All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92.
NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-alpha, IFN-gamma), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-kappaB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-kappaB activity and prevented IkappaBalpha degradation in a dose-dependent way, inhibited IFN-gamma production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo.
Li
Ang
A
School of life science, Tongji university, Shanghai 200092, PR China. liang3829@sina.com
He
Meilan
M
Wang
Hui
H
Qiao
Bin
B
Chen
Ping
P
Gu
Hua
H
Zhang
Mengjie
M
He
Shengxiang
S
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015870:Gene Expression; D053804:Granzymes / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*
D008562:Membrane Glycoproteins; C112260:NCR1 protein, human; D016328:NF-kappa B; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D007371:Interferon-gamma; D051550:I-kappa B Kinase; D053804:Granzymes