ArticleThe Journal of biological chemistry2010
Inhibition of secretion of interleukin (IL)-12/IL-23 family cytokines by 4-trifluoromethyl-celecoxib is coupled to degradation via the endoplasmic reticulum stress protein HERP.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- A double-blind, randomized controlled study of the effects of celecoxib on clinical symptoms and cognitive impairment in patients with drug-naïve first episode schizophrenia: pharmacogenetic impact of cyclooxygenase-2 functional polymorphisms.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- The active secretion of a subunit of IL-12 by tissue cells is regulated by Valosin-Containing Protein and intracellular calcium redistribution.bioRxiv : the preprint server for biology · 2026Article
- Functional Roles of N-Linked Glycosylation of Human Matrix Metalloproteinase 9.Traffic (Copenhagen, Denmark) · 2015Article
- LMAN1 (ERGIC-53) is a potential carrier protein for matrix metalloproteinase-9 glycoprotein secretion.Biochemical and biophysical research communications · 2015Article
- Do reciprocal interactions between cell stress proteins and cytokines create a new intra-/extra-cellular signalling nexus?Cell stress & chaperones · 2013Article
- A trifluoromethyl analogue of celecoxib exerts beneficial effects in neuroinflammation.PloS one · 2013Article
- A 4-trifluoromethyl analogue of celecoxib inhibits arthritis by suppressing innate immune cell activation.Arthritis research & therapy · 2012Article
- Endoplasmic reticulum stress: its role in disease and novel prospects for therapy.Scientifica · 2012Review
- The endoplasmic reticulum protein folding factory and its chaperones: new targets for drug discovery?British journal of pharmacology · 2011Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-12 (IL-12), p80, and IL-23 are structurally related cytokines sharing a p40 subunit. We have recently demonstrated that celecoxib and its COX-2-independent analogue 4-trifluoromethyl-celecoxib (TFM-C) inhibit secretion but not transcription of IL-12 (p35/p40) and p80 (p40/p40). This is associated with a mechanism involving altered cytokine-chaperone interaction in the endoplasmic reticulum (ER). In the present study, we found that celecoxib and TFM-C also block secretion of IL-23 (p40/p19 heterodimers). Given the putative ER-centric mode of these compounds, we performed a comprehensive RT-PCR analysis of 23 ER-resident chaperones/foldases and associated co-factors. This revealed that TFM-C induced 1.5-3-fold transcriptional up-regulation of calreticulin, GRP78, GRP94, GRP170, ERp72, ERp57, ERdj4, and ERp29. However, more significantly, a 7-fold up-regulation of homocysteine-inducible ER protein (HERP) was observed. HERP is part of a high molecular mass protein complex involved in ER-associated protein degradation (ERAD). Using co-immunoprecipitation assays, we show that TFM-C induces protein interaction of p80 and IL-23 with HERP. Both HERP siRNA knockdown and HERP overexpression coupled to cycloheximide chase assays revealed that HERP is necessary for degradation of intracellularly retained p80 by TFM-C. Thus, our data suggest that targeting cytokine folding in the ER by small molecule drugs could be therapeutically exploited to alleviate inappropriate inflammation in autoimmune conditions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.