Gene expression studies of a human monocyte cell line identify dissimilarities between differently manufactured glatiramoids

Sarah Kolitz, Tal Hasson, Fadi Towfic, Jason M. Funt, Shlomo Bakshi, Kevin D. Fowler, Daphna Laifenfeld, Augusto Grinspan, Maxim N. Artyomov, Tal Birnberg, Rivka Schwartz, Arthur Komlosh, Liat Hayardeny, David Ladkani, Michael R. Hayden, Benjamin Zeskind, Iris Grossman

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Glatiramer Acetate (GA) has provided safe and effective treatment for multiple sclerosis (MS) patients for two decades. It acts as an antigen, yet the precise mechanism of action remains to be fully elucidated, and no validated pharmacokinetic or pharmacodynamic biomarkers exist. In order to better characterize GA's biological impact, genome-wide expression studies were conducted with a human monocyte (THP-1) cell line. Consistent with previous literature, branded GA upregulated anti-inflammatory markers (e.g. IL10), and modulated multiple immune-related pathways. Despite some similarities, significant differences were observed between expression profiles induced by branded GA and Probioglat, a differently-manufactured glatiramoid purported to be a generic GA. Key results were verified using qRT-PCR. Genes (e.g. CCL5, adj. p < 4.1 × 10-5) critically involved in pro-inflammatory pathways (e.g. response to lipopolysaccharide, adj. p = 8.7 × 10-4) were significantly induced by Probioglat compared with branded GA. Key genes were also tested and confirmed at the protein level, and in primary human monocytes. These observations suggest differential biological impact by the two glatiramoids and warrant further investigation.

Original languageEnglish
Article number10191
JournalScientific reports
Volume5
DOIs
StatePublished - May 22 2015

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