Human hematopoietic cells express two forms of thecytokine receptor common γ-chain (γc)

Recent studies have revealed that the γ-chain of theIL-2 receptor is shared by the receptors for IL-4, IL7, IL-9, IL-13, and IL-15, and it is therefore also referred toas the common γ-chain (γc). Mutations of γc result inX-linked severe combined immunodeficiency syndrome inhumans, indicating that rye is essential for normal development and function of the immune system. We demonstratethat human hematopoietic cells express two γc transcriptsdiffering in their carboxyl terminal coding region. Onetranscript is the previously reported sequence (γc-long),whereas the newly identified sequence exhibits a deletion of72 nucleotides close to the 3’-end of the open reading frame(γc-short). This alteration predicts a loss of 24 amino acidsincluding a conserved tyrosine residue which is shared byseveral members of the cytokine receptor family. Thepresence of these two distinct forms of rye transcripts wasdemonstrated by sequencing of reversely transcribed andpolymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines andhuman peripheral blood lymphocytes. Furthermore, thetwo variants were present in peripheral blood lymphocytesfrom both female and male donors, which rules out allelicvariants since rye is a single copy gene located on the Xchromosome. A truncation mutant at a site near the observed changes in γc-short has been reported by othersto alter biochemical events activated by cytokines. Thiscombined with the loss of a potential SH2 "docking" sitein γc-short suggests that γc-long and γc-short may link todifferent signaling pathways and may play an importantrole in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.

Leptin: a multifunctional hormone

Leptin is the protein product encoded by the obese (ob)gene. It is a circulating hormone produced primarily by the adipose tissue. ob/ob mice with mutations of the gene encoding leptin become morbidly obese, infertile, hyperphagic, hypothermic,and diabetic. Since the cloning of leptin in 1994, our knowledge in body weight regulation and the role played by leptin has increased substantially. We now know that leptin signals through its receptor, OB-R, which is a member of the cytokine receptor superfamily. Leptin serves as an adiposity signal to inform the brain the adipose tissue mass in a negative feedback loop regulating food intake and energy expenditure. Leptin also plays important roles in angiogenesis, immune function, fertility and bone formation. Humans with mutations in the gene encoding leptin are also morbidly obese and respond to leptin treatment,demonstrating that enhancing or inhibiting leptin’s activities in vivo may have potential therapeutic benefits.

JAK-STAT pathway in carcinogenesis:Is it relevant to cholangiocarcinoma progression?

The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes, cholangiocarcinoma predisposition and development. Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.

Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

This study investigated whether bone marrow mesenchymal stem cell（BMSC） transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs（h BMSCs） were injected into the tail vein. Fourteen days later, we found that h BMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor（s EPOR） was injected into the lateral ventricle, and on the next 13 consecutive days. s EPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the h BMSCs ＋ s EPOR group than in the h BMSCs ＋ heat-denatured s EPOR group. The adhesive-removal test result and the modified Neurological Severity Scores（m NSS） were lower in the h BMSCs ＋ s EPOR group than in the heat-denatured s EPOR group. The adhesive-removal test result and m NSS were similar between the h BMSCs ＋ heat-denatured s EPOR group and the h BMSCs ＋ s EPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.

Effect of Bushenhuoxue formula on interleukin-1 beta and discoidin domain receptor 2 levels in a rat model of osteoarthritis

OBJECTIVE:To determine the effects of Bushenhuoxue formula(BHF) on interleukin-1 beta(IL-1β),transforming growth factor beta 1(TGF-β1),discoidin domain receptor 2(DDR2) and matrix metalloproteinase-1(MMP-1) levels in a rat model of osteoarthritis(OA).METHODS:Sprague-Dawley rats were used to establish an OA model and subjected to various treatments over 6 weeks.Rats were treated with BHF,glucosamine sulfate(G5),or starch as a control.Serum levels of IL-1β and MMP-1 and joint fluid levels of IL-1 β were determined by means of ELISAs.We used immunohistochemistry to determine DDR2 levels in knee cartilage.Gene expression levels of MMP-1 in joint synovial tissue were assessed using reverse transcription polymerase chain reaction assays.RESULTS:Serum IL-1β levels were unchanged throughout the study.Levels of IL-1β in joint fluid and MMP-1 in sera from the BHF- and GS-treated groups were significantly reduced.DDR2 levels in knee cartilage were also significantly reduced in the BHF group.Expression of the MMP-1 gene was significantly reduced by BHF treatment.CONCLUSION:BHF might be beneficial in the inhibition and alleviation of local inflammatory responses and cartilage degeneration in OA.

Responses of the Toll-like receptor and melanoma differentiation-associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks

Avian infectious bronchitis virus(IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3–5days post inoculation(dpi) and in the kidney at 8 dpi, with heavy viral loads at 1–11 and 1–28 dpi,respectively. The expression of m RNAs encoding Toll-like receptor(TLR) 3 and TLR7 were upregulated at 3–8 dpi, and that of TIR-domain-containing adapter-inducing interferon(IFN) β(TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88(My D88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor(TRAF) 3 and TRAF6 were upregulated expression in both tissues.Moreover, melanoma differentiation-associated protein 5(MDA5), laboratory of genetics and physiology 2(LGP2), stimulator of IFN genes(STING), and mitochondrial antiviral signaling protein(MAVS), as well as TANK binding kinase 1(TBK1), inhibitor of kappa B kinase(IKK) ?, IKKα, IKKβ,IFN regulatory factor(IRF) 7, nuclear factor of kappa B(NF-κB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β(MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally,consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.

The molecular mechanisms supporting the homeostasis and activation of dendritic epidermal T cell and its role in promoting wound healing

The epidermis is the outermost layer of skin and the first barrier against invasion.Dendritic epidermal T cells(DETCs)are a subset ofT cells and an important component of the epidermal immune microenvironment.DETCs are involved in skin wound healing,malignancy and autoim-mune diseases.DETCs secrete insulin-like growth factor-1 and keratinocyte growth factor for skin homeostasis and re-epithelization and release inflammatory factors to adjust the inflammatory microenvironment of wound healing.Therefore,an understanding of their development,activation and correlative signalling pathways is indispensable for the regulation of DETCs to accelerate wound healing.Our review focuses on the above-mentioned molecular mechanisms to provide a general research framework to regulate and control the function of DETCs.

New hypothesis and treatment targets of depression:an integrated view of key findings

Major depressive disorder（MDD） is a common and devastating psychiatric disorder characterized by persistent low mood,cognitive disorder,and impaired social function. Despite its complex mechanisms,increasing evidence has identified the involvement of neurotrophic factors,inflammatory cytokines,the hypothalamuspituitary-adrenal axis,and glutamate receptors in the pathophysiology of this illness. The present review synthesizes recent research achievements to defi ne the network between different hypotheses of MDD and to understand which part is most pivotal for its pathogenesis. By integrating MDD-related signal pathways,we highlight brain-derived neurotrophic factor（BDNF） dysfunction and increased apoptosis as the fi nal common cascades,and new therapeutic strategies aiming to enhance BDNF function have been shown to exert a rapid and effective antidepressant action.