IL can induce phagocytosis cytoskeleton rearrangement
IL-15 can induce phagocytosis, cytoskeleton rearrangement, gene expression, de novo protein synthesis and can delay apoptosis in human neutrophils . Production of chemokines, cytokines and natural inhibitors is increased in IL-15 induced neutrophils, including CXCL8 (IL-8) , IL-1beta, IL-1RII and IL-1Ra . IL-15 has also been shown to induce the redistribution of ICAM-3 and p-selectin glycoprotein ligand-1 (PSGL-1) to the uropods in neutrophil . The mechanisms involved in IL-15-induced activation of human neutrophils are not fully understood. However, IL-15 was shown to activate NFk-β , and to induce the phosphorylation of Syk and its physical association with IL15R-α .
Materials and methods
Discussion ENU is being used as a potent carcinogenic agent [28,29] which can induce several cancer including gingerol tumour , reproductive tumour , leukemia etc. in animal model. In this present study, BALB/c mice were used to induce leukemia by injecting ENU [32,33]. ENU, a carcinogen, can cause immune suppression in animal [34,35] and so the tumor load increased gradually in animal. To combat against tumor cells the manipulation is required to increase the number of normal immune cells in peripheral blood. G-CSF is a growth factor to proliferate and differentiate granulocyte cells. It is also reported that G-CSF can induce the expression of TLR9 to recognize pathogen . IL-15 has also important role in innate immune response. One of the major immunological responses of neutrophils is the phagocytic activity. Neutrophil has tumoricidal activity besides the phagocytosis to pathogen . TGF-β inhibition causes the tumoricidal activity of the neutrophil . By increasing the production of TNF-α, MIP1α, H2O2 and NO, neutrophil can kill the tumor cells in absence of TGF-β. Through tumor antibody dependent cell mediated cytotoxicity neutrophil can kill tumor cells though there are lacks of evidences for this activity. Our results showed that the phagocytic activity of neutrophils was down regulated in ENU induced leukemic mice probably due to inhibitory character of carcinogen and/or the lack of recognition of the tumor cells. This recognition is dependent on the expression of TLRs. In this study both TLR4 and TLR9 expression was significantly reduced in leukemic mice. In this study, in vitro phagocytosis activity was significantly reduced in the leukemia group. Also reduced number of neutrophils in ENU group interferes with the functional activity. But after the co-treatment with G-CSF and IL-15 in combination, phagocytic activity restored even more than control levels. Inducing tumor cells to release G-CSF, enhance the neutrophil population towards the tumor site and can regress the tumor load in vivo. Interleukin-15 plays a very crucial role in phagocytic activity of neutrophils by recruiting dendritic cells and generating cytotoxic T lymphocytes against cancer cells . Along with that, the ability of G-CSF to consistently induce white blood cell counts confirms its role as a potent hematopoietic growth factor, particularly for cells of the granulocytic lineage . Recent studies have suggested that human and mouse neutrophils used to kill target cells using TLRs, specially TLR4 and TLR9 as a mechanism of suppression and used in recent therapeutic approach .
Conflict of interest
Acknowledgements Project is funded by DBT as State biotech Hub; Grant No. BT/04/NE/2009 Dt 22-10-2010, Govt. of India. We are grateful to Dr. Nabyendu Murmu, CNCI, Kolkata for providing the Dalton\'s Lymphoma cell line, Sanjoy Nath, M.D. Department of Pathology, Tripura Medical College and BRAM Hospital, for the conformation of onset of leukemia.