Abstract
We have studied the immunomodulatory effects of interferon-alpha2b (IFN-alpha2b) in rectification of the dysregulated IFN-gamma-dependent chemokines and their receptor CXCR3 splice variants in head and neck squamous cell carcinoma-peripheral blood mononuclear cells (HNSCC-PBMC). CXCR3 expression was upregulated in HNSCC-PBMC, with the demonstration of poor chemotactic function. CXCR3 upregulation possibly represents the increased synthesis of CXCR3B splice variant, without significant change in CXCR3A. Upregulated expression of CXCR3B was downregulated following in vitro IFN-alpha2b treatment of HNSCC-PBMC. Upregulation of CXCR3A+B by IFN-alpha2b with downregulation of the CXCR3B indirectly suggests that the upregulation of the CXCR3A splice variant induces cellular migration. On the other hand, the stimulation of PBMC with IFN-alpha2b maintains physiological homeostasis of CXCR3 ligands, CXCL10 and CXCL9, and increases the secretion of IFN-gamma. The suppressed chemotactic ability of HNSCC-PBMC could be restored either by in vitro treatment of PBMC with IFN-alpha2b or during the use of IFN-alpha2b stimulated PBMC supernatant as a chemoattractant. Chemoattraction process is guided at the level of both receptor and its ligands, ...Continue Reading
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