Pseudoephedrine inhibits T-cell activation by targeting NF-kappaB, NFAT and AP-1 signaling pathways.
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Fiebich BL, Collado JA, Stratz C, Valina C, Hochholzer W, Munoz E, Bellido LM
Pseudoephedrine inhibits T-cell activation by targeting NF-kappaB, NFAT and AP-1 signaling pathways.
Immunopharmacol Immunotoxicol. 2012 Feb;34(1):98-106. doi: 10.3109/08923973.2011.582118. Epub 2011 Jun 2.
- PubMed ID
- 21631396 [ View in PubMed]
- Abstract
Pseudoephedrine (PSE) is a stereoisomer of ephedrine that is commonly used as a nasal decongestant in combination with other anti-inflammatory drugs for the symptomatic treatment of some common pathologies such as common cold. Herein, we describe for the first time the effects of PSE on T-cell activation events. We found that PSE inhibits interleukin-2 (IL-2) and tumor necrosis factor (TNF) alpha-gene transcription in stimulated Jurkat cells, a human T-cell leukemia cell line. To further characterize the inhibitory mechanisms of PSE at the transcriptional level, we examined the transcriptional activities of nuclear factor kappa B (NF-kappaB), nuclear factor of activated T cells (NFAT), and activator protein-1 (AP-1) transcription factors and found that PSE inhibited NF-kappaB-dependent transcriptional activity without affecting either the phosphorylation, the degradation of the cytoplasmic NF-kappaB inhibitory protein, IkappaBalpha or the DNA-binding activity. However, phosphorylation of the p65/RelA subunit was clearly inhibited by PSE in stimulated cells. In addition, PSE inhibited the transcriptional activity of NFAT without interfering with the calcium-induced NFAT dephosphorylation event, which represents the major signaling pathway for its activation. NFAT cooperates with c-Jun, a compound of the AP-1 complex, to activate target genes, and we also found that PSE inhibited both JNK activation and AP-1 transcriptional activity. These findings provide new mechanistic insights into the potential immunomodulatory activities of PSE and highlight their potential in designing novel therapeutic strategies to manage inflammatory diseases.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Pseudoephedrine activator protein 1 (Protein Group) Protein group Humans UnknownInhibitorDetails Pseudoephedrine Interleukin-2 Protein Humans UnknownInhibitorDetails Pseudoephedrine Nuclear factor NF-kappa-B p105 subunit Protein Humans UnknownInhibitorDetails Pseudoephedrine Nuclear factor of activated T-cells, cytoplasmic 1 Protein Humans UnknownInhibitorDetails Pseudoephedrine Tumor necrosis factor Protein Humans UnknownInhibitorDetails