Focused Screening Identifies Evoxine as a Small Molecule That Counteracts CO2-Induced Immune Suppression

Iiro Taneli Helenius, Aisha Nair, Humberto E Trejo Bittar, Jacob I. Sznajder, Peter H S Sporn, Greg J. Beitel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Patients with severe lung disease may develop hypercapnia, elevation of the levels of CO2 in the lungs and blood, which is associated with increased risk of death, often from infection. To identify compounds that ameliorate the adverse effects of hypercapnia, we performed a focused screen of 8832 compounds using a CO2-responsive luciferase reporter in Drosophila S2∗ cells. We found that evoxine, a plant alkaloid, counteracts the CO2-induced transcriptional suppression of antimicrobial peptides in S2∗ cells. Strikingly, evoxine also inhibits hypercapnic suppression of interleukin-6 and the chemokine CCL2 expression in human THP-1 macrophages. Evoxine's effects are selective, since it does not prevent hypercapnic inhibition of phagocytosis by THP-1 cells or CO2-induced activation of AMPK in rat ATII pulmonary epithelial cells. The results suggest that hypercapnia suppresses innate immune gene expression by definable pathways that are evolutionarily conserved and demonstrate for the first time that specific CO2 effects can be targeted pharmacologically.

Original languageEnglish (US)
Pages (from-to)363-371
Number of pages9
JournalJournal of Biomolecular Screening
Issue number4
StatePublished - Apr 1 2016


  • anti-infective drugs
  • cell-based assays
  • immune system diseases
  • reporter gene assays

ASJC Scopus subject areas

  • Drug Discovery
  • Analytical Chemistry
  • Molecular Medicine
  • Biochemistry
  • Biotechnology
  • Pharmacology


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