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

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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

Pseudoephedrine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pseudoephedrine	activator protein 1 (Protein Group)	Protein group	Humans	Unknown	Inhibitor	Details
Pseudoephedrine	Interleukin-2	Protein	Humans	Unknown	Inhibitor	Details
Pseudoephedrine	Nuclear factor NF-kappa-B p105 subunit	Protein	Humans	Unknown	Inhibitor	Details
Pseudoephedrine	Nuclear factor of activated T-cells, cytoplasmic 1	Protein	Humans	Unknown	Inhibitor	Details
Pseudoephedrine	Tumor necrosis factor	Protein	Humans	Unknown	Inhibitor	Details