{"doi":"10.1002/alr.23542","title":"Mediation of LPS‐Induced Inflammation With Pro‐Resolving Treatment in Human Nasal Polyps: A Pilot Study","abstract":"Chronic inflammation occurring in nasal polyp tissues also contains some degree of active tissue inflammatory resolution in epithelial and immune cell populations. Specialized pro-resolving mediators, such as resolvin D2, may mitigate inflammatory responses initiated by lipopolysaccharide exposure. Active inflammation resolution is a novel approach to chronic rhinosinusitis (CRS) management, and more research is required to examine cell-specific temporal effects of specialized-pro-resolving mediators in CRS tissues. Chronic rhinosinusitis (CRS) shares a common pathophysiology with other chronic inflammatory diseases, including periodic acute exacerbations and altered wound-healing processes [1]. A healthy sinonasal mucosal barrier relies on immune function to appropriately respond to airborne insults while choreographing a temporally regulated resolution of the acute physiological inflammatory response [2]. When this spatiotemporal response is disrupted, chronic inflammation may result as a potential contribution to etiopathogenesis or sustenance of inflammation in CRS. Nuclear factor-kappa B (NF-κB) signaling is one of several important contributors in the modulation of important inflammatory responses. It is recognized as an important transcription factor in the expression of various pro-inflammatory genes in chronic inflammatory diseases including CRS [3]. Lipid-derived molecules known as specialized-pro-resolving mediators (SPMs) [4] have recently been described as active components in temporal modulation of acute airway inflammatory responses and may play some role in the CRS disease process [5-7]. SPMs influence development, recruitment, and function of several inflammatory cells, including macrophages, dendritic cells, neutrophils, and lymphocytes [8]. In this study, we seek to understand SPM regulatory effects on NF-κB-associated pro-inflammatory genes using a fresh sinus tissue explant model. We hypothesize that SPM, resolvin D2 (RvD2), will mitigate lipopolysaccharide (LPS)-induced inflammation. Nasal polyp tissue was obtained via endoscopic sinus surgery at Indiana University School of Medicine (IRB #14784). Nasal polyp tissues were obtained from three subjects. All of these patients had clinical features of type 2 inflammatory disease, with either allergic rhinitis, asthma, or aspirin-exacerbated airway disease (Table S1). Tissues from the middle meatus and ethmoid sinus cavities were collected from patients. Upon harvest, specimens were immediately taken to the laboratory, serially rinsed with phosphate-buffered saline (PBS), and gently centrifuged to remove excess blood and mucus. Tissues were then preserved in 1:1 PBS and 10% dimethyl sulfoxide in liquid nitrogen. When preparing for experimental exposures, tissue was thawed and weighed. Plates were filled with 0.04 g tissue in 1 mL culture medium. Each sample was exposed to 10 µg/mL LPS, 50 nM RvD2, and 10 µg/mL LPS + 50 nM RvD2, or exclusively culture medium for 24 h ± 1 h. Tissue RNA was extracted and isolated, then cDNA was synthesized using a reverse transcription kit according to standard manufacturer protocol (see Supporting Information for additional details). A microarray NF-κB panel was used to amplify cDNA by real-time PCR. Fold increase was compared to control via ∆∆CT method, and those with the most significant differences were selected as candidate genes for further validation. To validate the effects of RvD2 on gene expression, qPCR for selected gene products was applied for CXCL1, G-CSF, and MYD88 in triplicate. qPCR was utilized to quantitatively assess the production of RNA in each of these genes with the same tissue samples used in PCR microarray. Statistical analysis was performed using GraphPad Prism. A paired t-test was performed to test the effects of SPM treatment with RvD2 for each inflammatory mediator. Multiple comparisons correction was applied between groups, and an alpha <0.05 was set for statistical significance. In the NF-κB microa","journal":"International Forum of Allergy & Rhinology","year":2025,"id":561901,"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":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1464083,"name":"Cristina Delgado","orcid":"0009-0005-0551-8479","position":1,"is_corresponding":false},{"id":497707,"name":"Karim Khan","orcid":"0000-0001-8689-9245","position":2,"is_corresponding":false},{"id":254434,"name":"Daniel N. Frank","orcid":"0000-0001-6669-228X","position":3,"is_corresponding":false},{"id":298602,"name":"Vijay R. Ramakrishnan","orcid":"0000-0003-2748-0705","position":4,"is_corresponding":false},{"id":1093261,"name":"Peyton Robinson","orcid":"0000-0002-0507-0900","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-19T02:56:01.883848Z","pmid":"39930908","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":[]}