Steroid hormone serving as an immunosuppressor often induces immunotoxicity when administered in highest dosage or accumulated in long-term usage. The stage of high concentration of steroid hormone leading to a wide range of symptoms is associated to the yang-deficient state,which is the part of yin-yang imbalance involved in processes of many diseases in traditional Chinese medicine. Here we intend to investigate the profile of Th1/Th2-related cytokine transcriptions under yang-deficient conditions in a yang-deficient animal model by intramuscular injection of hydrocortisone (a kind of steroid hormone). The yang-deficient symptoms were estimated by detecting activity,appetite,body weight and so on. T cell proliferation and cytokine transcriptions were analyzed. The results showed that yang-deficient mice were established successfully since typical yang-deficient symptoms were observed in this model with decreased activities,appetite,body weight and temperature. More interestingly,the transcriptions of IFN-γ,IL-2,IL-4 and IL-10 in this model were markedly suppressed and the proliferation of lymphocytes significantly decreased as well. The results suggested that yang-deficient symptoms were related to the steroid-induced reduction of cytokine transcription and impairment of lymphocyte proliferation. Therefore,novel strategies through regulating cytokine production might be considered as potent approach to patients with yang-deficiency symptoms.
HMBOX1 is a new member of the homeobox family.Homeobox members have been reported to participate in embryonic development and systemic metabolism,but the function of HMBOX1 remains unclear,especially in the hematopoietic system.Here,we show that HMBOX1is expressed at a high level in primary humanNKcells but is expressed at much lower levels inNKcell lines.Overexpression of HMBOX1 significantly inhibited NK cell activities,including natural cytotoxicity against tumor cells,the level of CD107a(a marker protein for degranulation)and the production of cytolytic proteins(perforin and granzymes).More interestingly,HMBOX1 negatively regulated the expression of NKG2D and the activation of the NKG2D/DAP10 signaling pathway in NK cells.This effect was reversed by knocking down HMBOX1.Taken together,these findings demonstrate that HMBOX1 may act as a negative regulator of NK cell functions via suppressing the NKG2D/DAP10 signaling pathway.
