Title:

Effect of Gli3 on Cytokine Expression In Monocytes

Waldenström Macroglobulinemia (WM) is a type of B-cell lymphoma that our lab currently focuses on. GLI3 is a transcription factor that is a member of the GLI family and is regulated by the hedgehog signaling pathway. GLI3’s most recognized role is in embryonic development and has been shown to play a role in various cancers as well. Prior research conducted by the Elsawa Lab has found that GLI3 may be correlated to the expression of inflammatory cytokines such as CCL2, IL-6 and TNF-𝛂. My research further explores the role of GLI3 in cytokine expression by comparing the relative expression of cytokines within human monocyte cell lines with and without GLI3 knocked down by use of a retrovirus. Interleukin-10 (IL-10) expression was significantly reduced within the GLI3 knocked down cell lines shown through RT-PCR analysis suggesting that GLI3 may play a role as a regulator for IL-10. IL-10 is a cytokine that has been found to affect CD4+ T-cells by inhibiting their ability to proliferate and perform antigen specific activation. Induction of B-cell proliferation is another function of IL-10. A possible immunotherapy for WM could be to target GLI3 to reduce the expression of IL-10, hopefully slowing the proliferation of the cancerogenic B-cells. CHip assays and an ELISA will be performed to further explore GLI3’s role in the expression of IL-10.

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