{"title":"SNHG16-loaded extracellular vesicles from hypoxic NSCLC cells drive M2 macrophage polarization to enhance cancer aggressiveness","authors":"Yanshen Hou , Ximing Li , Lingfei Zeng , Yuan Zhang","doi":"10.1016/j.molimm.2025.08.022","DOIUrl":"10.1016/j.molimm.2025.08.022","url":null,"abstract":"<div><div>Hypoxia plays a critical role in regulating the progression of non-small cell lung cancer (NSCLC) by modulating the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs), important components of TIME, can be regulated by hypoxic conditions. Unfortunately, the molecular mechanisms by which hypoxia regulates TAMs in TIME to affect NSCLC progression has not been fully delineated. The present study evidenced that hypoxia-stimulated NSCLC cells secreted extracellular vesicles (EVs) were featured with highly expressed small nucleolar RNA host gene 16 (SNHG16), and SNHG16-containing EVs (SNHG16-EVs) synergistically promoted cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties in NSCLC cells, and induced M2-polarization of macrophages in THP-1 cells through delivering SNHG16. Notably, M2-polarized macrophages were capable of enhancing cancer aggressiveness in NSCLC cells through secreting tumor-initiating cytokines, including interleukin-10 (IL-10), transforming growth factor β (TGF-β), and vascular endothelial-derived growth factor (VEGF). Mechanistically, it was found that SNHG16 sponged miR-132–3p to positively regulate its downstream target, kinesin family member 5 A (KIF5A), via a competing endogenous RNA (ceRNA) mechanism-dependent manner. Rescue experiments confirmed that SNHG16-EVs induced NSCLC progression and M2 polarization of THP-1 cells were all reversed by overexpressing miR-132–3p and silencing KIF5A. Collectively, hypoxia-stimulated NSCLC cells transferred SNHG16-containing EVs to promote cancer aggressiveness and M2-polarized macrophages in NSCLC through modulating the downstream miR-132–3p/KIF5A axis, and this study verified that targeting SNHG16-EVs may be a novel strategy to hamper NSCLC progression via modulating TME.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 66-79"},"PeriodicalIF":3.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Drice negatively regulates cellular and humoral immunity of Drosophila melanogaster","authors":"Priyanka Jaiswal, Madhu G. Tapadia","doi":"10.1016/j.molimm.2025.08.020","DOIUrl":"10.1016/j.molimm.2025.08.020","url":null,"abstract":"<div><div>The innate immune response is a double-edged sword in insects, comprising the humoral and cellular mechanisms to fight and eliminate pathogens. The humoral response is achieved by the production of antimicrobial peptides, which are secreted in the hemolymph. The cellular responses are mediated by phagocytosis, encapsulation and melanization. Though the fat bodies are the primary immune tissues in <em>Drosophila,</em> secreting AMPs, the Malpighian tubules are also autonomous immune organs that constitutively secrete AMPs at basal levels, which increases after infection. Here we provide evidence to show that the caspase 3 homolog in <em>Drosophila</em>, Drice, negatively regulates both, cellular as well as humoral immunity. Depletion of Drice leads to the increased expression of transcription factor Relish, which enhances the expression of certain AMPs regulated by the IMD pathway. In the absence of Drice, both the Ecdysone receptor- B1 and Broad-core (Br-C) are also upregulated which are upstream regulators of the IMD pathway. The increase in crystal cells clearly indicates Drice to be a negative regulator of this form of cellular immunity. Collectively our findings suggest the role of Drice in the immune regulation of <em>Drosophila melanogaster</em>, and these results will add to the growing understanding of diverse roles of caspases in immune regulation.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 61-65"},"PeriodicalIF":3.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaiyue Wang , Qiao Gu , Chunyan Xue , Junyu Shi , Kun Wang , Xiaozhou He
{"title":"MAP30 inhibits proliferation and metastasis of bladder cancer by increasing EGR1 expression and promoting the transcriptional activation of DUSP1","authors":"Kaiyue Wang , Qiao Gu , Chunyan Xue , Junyu Shi , Kun Wang , Xiaozhou He","doi":"10.1016/j.molimm.2025.08.024","DOIUrl":"10.1016/j.molimm.2025.08.024","url":null,"abstract":"<div><div>The confirmed tumor-inhibitory effects of the 30 kDa Momordica anti-human immunodeficiency virus protein (MAP30) have yet to be complemented by an exploration into its mechanism of action on tumor development and metastasis. For this purpose, we delved into the intrinsic mechanism of MAP30 in bladder cancer (BC). Here, we demonstrated that MAP30 markedly suppressed the proliferation, migration, invasion, and angiogenic capabilities of human BC cells <em>in vitro</em>, and the tumor metastatic potential <em>in vivo</em>. Furthermore, our findings showed that MAP30 suppressed the functional activities of BC cells by upregulating the expression levels of early growth response 1 (EGR1). Additionally, our investigation confirmed that EGR1 and dual specificity phosphatase 1 (DUSP1) were down-expressed in BC and had been identified as closely linked to the advancement of BC. DUSP1 was transcriptionally induced by EGR1, and the expression of EGR1 was found to be positively linked with DUSP1 in human BC tissues. The knockdown of EGR1 was found to boost cell invasion, migration, proliferation, and angiogenesis via the MAPK signaling pathway, however, the overexpression of DUSP1 inhibited EGR1 knockdown-induced promotion of these functional activities in BC cells. Furthermore, MAP30 inhibited the invasion, migration, proliferation, and angiogenesis of BC cells by regulating the EGR1-DUSP1 axis. Our study yielded an exhaustive insight into the suppressive actions of MAP30 on BC progression.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 48-60"},"PeriodicalIF":3.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lichun Zhao, Peixin Shi, Yujiao Zhang, Mingxuan Zhang, Na Han, Zhihui Liu, Sikai Li, Jun Yin, Jianxiu Zhai
{"title":"Study on the adjuvant activity and mechanism of action of a novel Monophosphoryl Lipid A","authors":"Lichun Zhao, Peixin Shi, Yujiao Zhang, Mingxuan Zhang, Na Han, Zhihui Liu, Sikai Li, Jun Yin, Jianxiu Zhai","doi":"10.1016/j.molimm.2025.08.019","DOIUrl":"10.1016/j.molimm.2025.08.019","url":null,"abstract":"<div><div>In order to develop a novel vaccine adjuvant that is highly efficient, cost-effective, and suitable for widespread application, this study employed synthetic biology techniques to produce a new type of <em>Escherichia coli</em> monophosphate lipid A (N-MPL). Specifically, the phosphate group attached to the C-1 position was removed, and a hydroxyl group was introduced into the 3′-secondary fatty acid chain of the original lipid A structure. This modification aimed to reduce toxicity while enhancing water solubility. Two formulations of N-MPL were prepared and their immunological and adjuvant activities were evaluated. Results demonstrated that both formulations could promote the proliferation of immune cells and the maturation of bone marrow-derived dendritic cells (BMDCs). In an adjuvant immunization experiment using H1N1 vaccine in ICR mice, N-MPL exhibited superior adjuvant effects compared to aluminum adjuvants and commercially available Monophosphoryl Lipid A (Synthetic) (PHAD™). Through comprehensive analysis of splenic lymphocytes, antibodies, cytokines, and immune factors in immunized mice, it was discovered for the first time that different formulations of N-MPL adjuvants could regulate cellular and humoral immunity, albeit with distinct foci of induced immune responses. The oil-in-water formulation of N-MPL primarily induced cellular immune responses in mice, whereas the aqueous solution formulation predominantly elicited humoral immune responses. Mechanistic studies revealed that N-MPL regulates the Th1/Th2 response via the TLR4-MyD88-NF-κB signaling pathway. Overall, the novel N-MPL adjuvant exhibits high efficiency and low cost, demonstrating significant potential for vaccine adjuvant development.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 28-47"},"PeriodicalIF":3.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qianning Li , Yucheng Tu , Hengyi Diao , Linli Zheng , Weishen Chen
{"title":"SMAD7-mediated ferroptosis in macrophages drives osteoporosis progression: A multi-omics study","authors":"Qianning Li , Yucheng Tu , Hengyi Diao , Linli Zheng , Weishen Chen","doi":"10.1016/j.molimm.2025.08.021","DOIUrl":"10.1016/j.molimm.2025.08.021","url":null,"abstract":"<div><div>Osteoporosis (OP) is characterized by imbalanced bone homeostasis, which is difficult to precisely regulate with current therapeutic strategies. Macrophages play a significant role in bone remodeling due to their complex interactions with osteoclasts and osteoblasts, suggesting that targeting macrophage-related pathways could offer novel therapeutic opportunities. To explore this, we combined bulk RNA-seq and scRNA-seq data to identify macrophage-related genes. Using bioinformatic tools, including CIBERSORT, WGCNA, and machine learning algorithms, we identified 1705 macrophage marker genes and 839 macrophage module genes. Enrichment analysis revealed that the intersection genes were significantly enriched in the ferroptosis signaling pathway, highlighting its critical role in macrophages. Further validation through protein-protein interaction networks and cellular communication analysis confirmed the importance of ferroptosis in macrophage. Using artificial neural network, we identified 4 macrophage hub genes, with SMAD7 showing the greatest weight. Experimental validation using RAW264.7 cells, immunohistochemistry, and micro-CT analysis further demonstrated the association of ferroptosis-related indicators (Fe<sup>2 +</sup> and lipid peroxidation) with bone damage in osteoporosis patients. And we found SMAD7 showing the strongest correlation with trabecular microstructural deterioration. Notably, our findings also confirmed that the SMAD7 inhibitor mongersen effectively attenuated macrophage ferroptosis, suggesting its potential to improve bone microstructural integrity. Our study demonstrates that SMAD7-mediated macrophage ferroptosis is a critical mechanism in osteoporosis pathogenesis, highlighting SMAD7 as a promising therapeutic target.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 11-27"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoli Liu , Jie Liang , Lizhen Zhao , Wei Li , Luoyang Wang , Xiao Wang , Yi Liu , Mengting Zhou , Xinqiang Li , Zhuoyu Jia , Meiying Song , Li Zhang , Yanyan Yang , Jinzhen Cai , Bei Zhang
{"title":"CCL5: An emerging key target and progress in the targeted therapy of hepatocellular carcinoma","authors":"Xiaoli Liu , Jie Liang , Lizhen Zhao , Wei Li , Luoyang Wang , Xiao Wang , Yi Liu , Mengting Zhou , Xinqiang Li , Zhuoyu Jia , Meiying Song , Li Zhang , Yanyan Yang , Jinzhen Cai , Bei Zhang","doi":"10.1016/j.molimm.2025.08.023","DOIUrl":"10.1016/j.molimm.2025.08.023","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a highly prevalent and lethal malignancy, presenting significant challenges in clinical diagnosis and treatment. The chemokine C-C motif ligand 5 (CCL5) plays a pivotal role in HCC pathogenesis. While traditionally viewed primarily as a mediator of immune cell chemotaxis and migration, recent evidence demonstrates that CCL5 directly influences tumor cells, regulating malignant behaviors such as proliferation and invasion. Furthermore, CCL5 recruits diverse immune cells, including immunosuppressive populations, to the tumor microenvironment (TME), remodeling the TME and exerting context-dependent effects that can either promote immune evasion or enhance anti-tumor immunity. This article reviews advances in understanding the mechanisms of CCL5 in HCC and discusses the translational potential of targeting CCL5 for HCC therapy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qiufen Yang , Huiliang Ji , Amir Modarresi Chahardehi
{"title":"JAK/STAT pathway in myocardial infarction: Crossroads of immune signaling and cardiac remodeling","authors":"Qiufen Yang , Huiliang Ji , Amir Modarresi Chahardehi","doi":"10.1016/j.molimm.2025.08.018","DOIUrl":"10.1016/j.molimm.2025.08.018","url":null,"abstract":"<div><div>Myocardial infarction (MI) initiates a robust immune-inflammatory response in which dysregulated cytokine signaling exacerbates tissue damage and adverse cardiac remodeling. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway serves as a key mediator of cytokine signaling and immune cell activation, playing a dual role in post-MI outcomes. On one hand, JAK/STAT activation supports cardioprotective mechanisms such as angiogenesis and anti-apoptotic signaling; on the other hand, its excessive or prolonged activation contributes to maladaptive inflammation, fibrosis, and heart failure. This review examines how pro-inflammatory cytokines (e.g., IL-6, TNF-α) and immune cells (e.g., macrophages, neutrophils) activate the JAK/STAT pathway in ischemic myocardium. We discuss the pathway’s crosstalk with inflammatory signaling networks, including NF-κB, MAPK, and PI3K/Akt, and evaluate the potential of repurposing JAK inhibitors (e.g., ruxolitinib) to modulate immune responses after MI, drawing insights from clinical trials in autoimmune diseases. Unresolved challenges such as cell-specific effects of JAK/STAT modulation and the need for biomarker-driven therapies are also highlighted. By synthesizing current preclinical and clinical evidence, this review proposes a framework for immune-targeted strategies aimed to improving cardiac outcomes following MI.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 206-217"},"PeriodicalIF":3.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Youjun Rong , Jianfeng Pan , Shuran Niu , Xiaofang Ao , Yihan Wang , Fangzheng Shang , Qi Lv , Zhiying Wang , Ruijun Wang , Rui Su , Yanhong Zhao , Yu Wang , Yanjun Zhang
{"title":"The circERBB3/chi-miR-181b-5p/TNFSF11 axis regulates proliferation, migration, and apoptosis in cashmere goat embryonic fibroblasts","authors":"Youjun Rong , Jianfeng Pan , Shuran Niu , Xiaofang Ao , Yihan Wang , Fangzheng Shang , Qi Lv , Zhiying Wang , Ruijun Wang , Rui Su , Yanhong Zhao , Yu Wang , Yanjun Zhang","doi":"10.1016/j.molimm.2025.08.001","DOIUrl":"10.1016/j.molimm.2025.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Inner Mongolia cashmere goat is an excellent local variety of both cashmere and meat. Its cashmere is delicate and soft and has high economic value. The morphogenesis and development of hair follicles directly affect the wool yield and quality of cashmere goats. Circular RNAs are endogenous, non-coding RNAs found in eukaryotic genomes that are involved in a variety of physiological and pathological processes. However, the potential function of circRNA in the development of embryonic skin hair follicles in cashmere goats remains unknown.</div></div><div><h3>Results</h3><div>In this study, we identified a novel circular RNA, circERBB3, isolated fibroblasts from cashmere goat embryonic skin tissue, and investigated its role in fibroblast proliferation, apoptosis, and migration. The interaction between circERBB3, chi-miR-181b-5p, and <em>TNFSF11</em> was detected by bioinformatics, real-time quantitative PCR, and the dual luciferase reporter gene system. Mechanistically, we demonstrated the functional significance of circERBB3 by interfering with circERBB3 in fibroblasts. At the molecular and cellular levels, co-transfection tests confirmed that circERBB3 negatively regulated fibroblast proliferation, apoptosis, and migration in a chi-miR-181b-5p-dependent manner. Chi-miR-181b-5p can regulate the proliferation, apoptosis, and migration of fibroblasts by targeting <em>TNFSF11</em>.</div></div><div><h3>Conclusions</h3><div>As a competitive endogenous RNA, circERBB3 binds to chi-miR-181b-5p and alleviates the inhibition of its target gene, <em>TNFSF11</em>, to regulate the proliferation, apoptosis, and migration of embryonic fibroblasts in cashmere goats. A new regulatory pathway regulating the development of hair follicles was revealed.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 174-185"},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Luo , Sanja Milkovska-Stamenova , Julia Karbach , Elke Jäger , Ralf Hoffmann , Jörg Gabert
{"title":"An indirect ELISA for the detection of anti-NY-ESO-1 antibodies in cancer patients and for monitoring cancer therapy","authors":"Ji Luo , Sanja Milkovska-Stamenova , Julia Karbach , Elke Jäger , Ralf Hoffmann , Jörg Gabert","doi":"10.1016/j.molimm.2025.08.009","DOIUrl":"10.1016/j.molimm.2025.08.009","url":null,"abstract":"<div><div>Early diagnosis of cancer offers the best chance for effective treatment. Serological tests for the detection of cancer testis antigens (CTA) could aid in cancer diagnosis, prognosis, and treatment evaluation. Since NY-ESO-1 induces a strong immune response in several cancer types, it is considered an attractive CTA for antibody assay development. The full-length NY-ESO-1 protein was recombinantly produced in <em>Escherichia coli</em>, purified, and used to develop an indirect enzyme-linked immunosorbent assay (ELISA) for the detection of NY-ESO-1 specific antibodies. This ELISA was optimized and validated using serum samples collected from 78 confirmed cancer patients and control sera from healthy donors (n = 20) and rheumatoid arthritis patients (n = 43). The optimized NY-ESO-1 ELISA provided a sensitivity of 96.2 % in cancer patients and a specificity of 100 % for non-cancer donors. A follow-up study of patients undergoing cancer treatment indicated that the antibody levels were responsive to therapy, becoming very low or negative after successful treatment and rising again before tumor metastasis recurrence was confirmed. Comparative peptide ELISA using overlapping peptides of the full NY-ESO-1 sequence did not improve the detection rate, but did reveal common epitopes. The NY-ESO-1 protein-based ELISA could be used to detect potential cancer patients and is useful for monitoring cancer therapy and tumor recurrence after treatment.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 186-192"},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Wang , Wenting Huang , Liang Long , Peng Fu , Qiongping Wang , Fa Long , Shengming Liu
{"title":"Curcumin modulates tracheal epithelial cell autophagy in asthma by inhibiting the NF-κB pathway via SCGB3A2","authors":"Tao Wang , Wenting Huang , Liang Long , Peng Fu , Qiongping Wang , Fa Long , Shengming Liu","doi":"10.1016/j.molimm.2025.08.012","DOIUrl":"10.1016/j.molimm.2025.08.012","url":null,"abstract":"<div><h3>Background and objective</h3><div>Asthma, a chronic inflammatory airway disease, presents a significant global health burden. This study aimed to elucidate the mechanism by which curcumin modulates tracheal epithelial cell autophagy in asthma, with a specific focus on its interplay with SCGB3A2 and the NF-κB pathway.</div></div><div><h3>Methods</h3><div>An <em>in vitro</em> asthma model was mimicked using 16HBE cells treated with TDI. Concurrently, a TDI-induced asthma model was built in Balb/c mice for <em>in vivo</em> investigations. Cells or mice were subjected to curcumin treatment, and SCGB3A2 was knockdown or overexpressed, to explore the function of SCGB3A2. TNF-α and TPCA-1 were also utilized to mediate activation of NF-κB <em>in vitro</em>. Western blot, qPCR, ELISA, immunofluorescence, and transmission electron microscopy were employed to assess SCGB3A2 expression, NF-κB pathway activation, autophagy, key inflammatory cytokines, and airway remodeling indicators.</div></div><div><h3>Results</h3><div>TDI stimulation reduced SCGB3A2 expression in 16HBE cells. SCGB3A2 overexpression mitigated TDI-induced inflammation and airway remodeling by inhibiting the NF-κB pathway and enhancing autophagy. Subsequent NF-κB activation partially abrogated these SCGB3A2-mediated protective effects on inflammation, airway remodeling, and autophagy. Curcumin treatment upregulated SCGB3A2, inhibited NF-κB activation, and promoted autophagy; these protective effects were substantially diminished upon SCGB3A2 knockdown. <em>In vivo</em>, curcumin administration ameliorated asthma features, evidenced by reduced airway inflammation, suppressed NF-κB, and enhanced autophagy in tracheal epithelial tissues.</div></div><div><h3>Conclusions</h3><div>This study reveals that curcumin protects against asthma by modulating the SCGB3A2-NF-κB-autophagy axis. These findings highlight this axis as a novel therapeutic target for asthma.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"Pages 193-205"},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}