{"doi":"10.17615/8se8-0n63","title":"15-Deoxy-Δ 12,14 -prostaglandin J 2 -mediated ERK Signaling Inhibits Gram-negative Bacteria-induced RelA Phosphorylation and Interleukin-6 Gene Expression in Intestinal Epithelial Cells through Modulation of Protein Phosphatase 2A Activity","abstract":"We have previously shown that non-pathogenic Gram-negative Bacteroides vulgatus induces transient RelA phosphorylation (Ser-536), NF-kappaB activity, and pro-inflammatory gene expression in native and intestinal epithelial cell (IEC) lines. We now demonstrate that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) but not prostaglandin E(2) inhibits lipopolysaccharide (LPS) (B. vulgatus)/LPS (Escherichia coli)-induced RelA phosphorylation and interleukin-6 gene expression in the colonic epithelial cell line CMT-93. This inhibitory effect of 15d-PGJ(2) was mediated independently of LPS-induced IkappaBalpha phosphorylation/degradation and RelA nuclear translocation as well as RelA DNA binding activity. Interestingly, although B. vulgatus induced nuclear expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in native epithelium of monoassociated Fisher rats, PPARgamma-specific knock-down in CMT-93 cells using small interference RNA failed to reverse the inhibitory effects of PPARgamma agonist 15d-PGJ(2), suggesting PPARgamma-independent mechanisms. In addition, 15d-PGJ(2) but not the synthetic high affinity PPARgamma ligand rosiglitazone triggered ERK1/2 phosphorylation in IEC, and most importantly, MEK1 inhibitor PD98059 reversed the inhibitory effect of 15dPGJ(2) on LPS-induced RelA phosphorylation and interleukin-6 gene expression. Calyculin A, a specific phosphoserine/phospho-threonine phosphatase inhibitor increased the basal phosphorylation of RelA and reversed the inhibitory effect of 15d-PGJ(2) on LPS-induced RelA phosphorylation. We further demonstrated in co-immunoprecipitation experiments that 15d-PGJ(2) triggered protein phosphatase 2A activity, which directly dephosphorylated RelA in LPS-stimulated CMT-93 cells. We concluded that 15d-PGJ(2) may help to control NF-kappaB signaling and normal intestinal homeostasis to the enteric microflora by modulating RelA phosphorylation in IEC through altered protein phosphatase 2A activity.","journal":"UNC Libraries","year":2021,"id":230258,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":836060,"name":"Pedro A. Ruiz","orcid":"0000-0001-7528-1474","position":1,"is_corresponding":false},{"id":413083,"name":"Sandra C. Kim","orcid":"0009-0005-3302-7589","position":2,"is_corresponding":false},{"id":262529,"name":"Dirk Haller","orcid":"0000-0002-6977-4085","position":3,"is_corresponding":false},{"id":36349,"name":"R. Balfour Sartor","orcid":"0000-0002-7820-632X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:05.844766Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}