Guanylate binding protein1 alters expression of the poly I: C induced cytokines/chemokines and MAP kinases in macrophages.

Guanylate binding protein 1 (GBP1) is critical in the host's innate immune response against viral infections and inflammation. Therefore, this study explored the role of GBP1 poly I: C, a synthetic analog of double-stranded RNA that mimics viral infections-induced inflammation in macrophages. Stimulation of human macrophage THP-1 and mice macrophage RAW 264.7 cell lines with 1 μg/ml of poly I: C revealed differential expression patterns of GBP1 to GBP7. Further, to know the specific role of GBP1in poly I: C induced inflammation, GBP1 gene was silenced in these two macrophage cells using small interfering RNA (siRNA), leading to significant reductions in GBP1 mRNA and protein levels. Further, the expression of key cytokines (IFN-γ, TNF-α, IL-4, IL-10, and IL-12b) and chemokines (CXCL9, CXCL10, CXCL11) after poly I: C treatment resulted in altered cytokine and chemokine expression profiles. Additionally, increased phosphorylation of ERK1/2, p38, and STAT1 transcription factors was observed in GBP1 knockdown cells. No change in the expression level of c-Jun and NF-kB was observed in response to poly I: C in GBP1 silenced cells compared to control cells. These findings provide valuable insights into the crosstalk/connection of GBP1 in poly I: C-induced immune responses in macrophages.