Inflammation Research最新文献

{"title":"Olink proteomics and lipidomics analysis of serum from patients infected with non-tuberculous mycobacteria and Mycobacterium tuberculosis.","authors":"Li Wang, Guoling Yang, Liang Guo, Lan Yao, Yidian Liu, Wei Sha","doi":"10.1007/s00011-024-01943-z","DOIUrl":"10.1007/s00011-024-01943-z","url":null,"abstract":"<p><strong>Background: </strong>Non-tuberculous mycobacterial (NTM) and Mycobacterium tuberculosis (MTB) infections are difficult to diagnose and treat, significantly burdening global health. The host immune status is generally believed to be associated with the onset and progression of NTM and MTB infections, but its specific impact remains unclear.</p><p><strong>Methods: </strong>In the present study, proteomics and lipidomics analysis of serum from normal controls (n = 26) and patients with MTB (n = 26), rapidly growing NTM (RGM, n = 15), and slowly growing NTM (SGM, n = 21) were conducted using the Olink technique based on a highly sensitive and specific neighborhood extension assay and the lipidomics technique.</p><p><strong>Results: </strong>IFN-γ, CXCL9, CXCL10, CXCL11, and CXCL13, etc. were simultaneously upregulated in MTB, RGM, and SGM, while lipids FAHFA 22:3, FAHFA 26:4, FAHFA 24:4, FAHFA 20:5, FAHFA 18:2 simultaneously downregulated. IL8, CCL3, CXCL5, and MCP-2, etc. were simultaneously upregulated in RGM and SGM compared to MTB, as well as PCs, LPCs, PEs, and LPEs. Compared with RGM, IL7, CD27, CCL17, CXCL12, and LPC 28:7-SN2 were downregulated in SGM. Pathway analyses revealed that tuberculosis, sphingolipid signaling pathway, and adipocytokine signaling pathway were regulated at the protein level and metabolite level. Diagnostic panels comprising immune-associated proteins and lipids greatly enhance diagnostic specificity and sensitivity.</p><p><strong>Conclusion: </strong>This integrated multi-omics analysis provides a more comprehensive understanding of the molecular landscape of NTM and MTB, which may provide molecular targets for specialized therapies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1945-1960"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma.","authors":"Narjes Saheb Sharif-Askari, Bushra Mdkhana, Shirin Hafezi, Bariaa A Khalil, Baraa Khalid Al-Sheakly, Hala Halwani, Fatemeh Saheb Sharif-Askari, Rabih Halwani","doi":"10.1007/s00011-024-01937-x","DOIUrl":"10.1007/s00011-024-01937-x","url":null,"abstract":"<p><strong>Background: </strong>Calprotectin, a calcium-binding protein, plays a crucial role in inflammation and has been associated with various inflammatory diseases, including asthma. However, its regulation and impact on steroid hyporesponsiveness, especially in severe asthma, remain poorly understood.</p><p><strong>Methods: </strong>This study investigated the regulation of calprotectin proteins (S100A8 and S100A9) by IL-17 and its role in steroid hyporesponsiveness using in vitro and in vivo models. Calprotectin expression was assessed in primary bronchial fibroblasts from healthy controls and severe asthmatic patients, as well as in mouse models of steroid hyporesponsive lung inflammation induced by house dust mite (HDM) allergen and cyclic-di-GMP (cdiGMP) adjuvant. The effects of IL-17A stimulation on calprotectin expression and steroid response markers in bronchial epithelial and fibroblast cells were examined. Additionally, the therapeutic potential of paquinimod, a calprotectin inhibitor, in mitigating airway inflammation and restoring steroid response signatures in the mouse model was evaluated.</p><p><strong>Results: </strong>The results demonstrated upregulation of calprotectin expression in asthmatic bronchial fibroblasts compared to healthy controls, as well as in refractory asthma samples compared to non-refractory asthma. IL-17 stimulation induced calprotectin expression and dysregulated glucocorticoid response signatures in lung epithelial and fibroblast cells. Treatment with paquinimod reversed IL-17-induced dysregulation of steroid signatures, indicating the involvement of calprotectin in this process. In the HDM/cdiGMP mouse model, paquinimod significantly attenuated airway inflammation and hyperresponsiveness, and restored steroid response signatures, whereas dexamethasone showed limited efficacy. Mechanistically, paquinimod inhibited MAPK/ERK and NF-κB pathways downstream of calprotectin, leading to reduced lung inflammation.</p><p><strong>Conclusion: </strong>These findings highlight calprotectin as a potential therapeutic target regulated by IL-17 in steroid hyporesponsive asthma. Targeting calprotectin may offer a promising approach to alleviate airway inflammation and restore steroid responsiveness in severe asthma. Further investigations are warranted to explore its therapeutic potential in clinical settings and elucidate its broader implications in steroid mechanisms of action.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1875-1888"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106952","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":"Plant extracts and omega-3 supplementation modulate hippocampal oxylipin profile in response to LPS-induced neuroinflammation.","authors":"Marie Martin, Emie Debenay, Jeanne Bardinet, Adrien Peltier, Line Pourtau, David Gaudout, Sophie Layé, Véronique Pallet, Anne-Laure Dinel, Corinne Joffre","doi":"10.1007/s00011-024-01947-9","DOIUrl":"10.1007/s00011-024-01947-9","url":null,"abstract":"<p><strong>Objective and design: </strong>Neuroinflammation is a protective mechanism but can become harmful if chronic and/or unregulated, leading to neuronal damage and cognitive alterations. Limiting inflammation and promoting resolution could be achieved with nutrients such as grapes and blueberries polyphenols, saffron carotenoids, and omega-3, which have anti-inflammatory and proresolutive properties.</p><p><strong>Methods: </strong>This study explored the impact of 18-day supplementation with plant extracts (grape, blueberry and saffron), omega-3 or both (mix) on neuroinflammation induced by lipopolysaccharide (LPS, 250 µg/kg) in 149 mice at different time points post-LPS treatment (30 min, 2 h, 6 h). Inflammatory, oxidative and neuroprotective gene expression; oxylipin quantification; and fatty acid composition were analyzed at each time point. PCA analysis was performed with all these biomarkers.</p><p><strong>Results: </strong>Mix supplementation induced changes in the resolution of inflammation. In fact, the production of proinflammatory mediators in the hippocampus started earlier in the supplemented group than in the LPS group. Pro-resolving mediators were also found in higher quantities in supplemented mice. These changes were associated with increased hippocampal antioxidant status at 6 h post-LPS.</p><p><strong>Conclusions: </strong>These findings suggest that such dietary interventions with plant extracts, and omega-3 could be beneficial in preventing neuroinflammation and, consequently, age-related cognitive decline. Further research is needed to explore the effects of these supplements on chronic inflammation in the context of aging.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"2023-2042"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic nucleotides increase IL-10 expression in airway macrophages to mitigate airway allergy.","authors":"Jinmei Xue, Zhizhen Liu, Bailing Xie, Rui Dong, Juan Wu, Yisha Wu, Zhihan Xu, Yuhe Tian, Yao Wei, Zhigang Geng, Lei Lu, Yu Liu, Jun Xie, Pingchang Yang","doi":"10.1007/s00011-024-01940-2","DOIUrl":"10.1007/s00011-024-01940-2","url":null,"abstract":"<p><strong>Background: </strong>Dysfunctional immune regulation plays a crucial role in the pathogenesis of airway allergies. Macrophages are one of the components of the immune regulation cells. The aim of this study is to elucidate the role of lysine demethylase 5 A (KDM5A) in maintaining macrophages' immune regulatory ability.</p><p><strong>Methods: </strong>DNA was extracted from Lactobacillus rhamnosus GG to be designated as LgDNA. LgDNA was administered to the mice through nasal instillations. M2 macrophages (M2 cells) were isolated from the airway tissues using flow cytometry.</p><p><strong>Results: </strong>We found that airway M2 cells of mice with airway Th2 polarization had reduced amounts of IL-10 and KDM5A. Mice with Kdm5a deficiency in M2 cells showed the airway Th2 polarization. The expression of Kdm5a in airway M2 cells was enhanced by nasal instillations containing LgDNA. KDM5A mediated the effects of LgDNA on inducing the Il10 expression in airway M2 cells. Administration of LgDNA mitigated experimental airway allergy.</p><p><strong>Conclusions: </strong>M2 macrophages in the airway tissues of mice with airway allergy show low levels of KDM5A. By upregulating KDM5A expression, LgDNA can increase Il10 expression and reconcile airway Th2 polarization.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1919-1930"},"PeriodicalIF":4.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132621","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":"The role of Pim-1 kinases in inflammatory signaling pathways.","authors":"Hye Suk Baek, Nacksung Kim, Jong Wook Park, Taeg Kyu Kwon, Shin Kim","doi":"10.1007/s00011-024-01924-2","DOIUrl":"10.1007/s00011-024-01924-2","url":null,"abstract":"<p><strong>Objective and design: </strong>This observational study investigated the regulatory mechanism of Pim-1 in inflammatory signaling pathways.</p><p><strong>Materials: </strong>THP-1, RAW 264.7, BV2, and Jurkat human T cell lines were used.</p><p><strong>Treatment: </strong>None.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS) was used to induce inflammation, followed by PIM1 knockdown. Western blot, immunoprecipitation, immunofluorescence, and RT-PCR assays were used to assess the effect of PIM1 knockdown on LPS-induced inflammation.</p><p><strong>Results: </strong>PIM1 knockdown in macrophage-like THP-1 cells suppressed LPS-induced upregulation of pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, phosphorylated Janus kinase, signal transducer and activator of transcription 3, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B p65 (NF-κB p65). It also suppressed upregulation of inhibitor of NF-κB kinase α/β and enhanced the nuclear translocation of NF-κB p65. Moreover, it inhibited the upregulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and cleavage of caspase-1 induced by co-treatment of LPS with adenosine triphosphate. Additionally, p-transforming growth factor-β-activated kinase 1 (TAK1) interacted with Pim-1. All three members of Pim kinases (Pim-1, Pim-2, and Pim-3) were required for LPS-mediated inflammation in macrophages; however, unlike Pim-1 and Pim-3, Pim-2 functioned as a negative regulator of T cell activity.</p><p><strong>Conclusions: </strong>Pim-1 interacts with TAK1 in LPS-induced inflammatory responses and is involved in MAPK/NF-κB/NLRP3 signaling pathways. Additionally, considering the negative regulatory role of Pim-2 in T cells, further in-depth studies on their respective functions are needed.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1671-1685"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RIP3 regulates doxorubicin-induced intestinal mucositis via FUT2-mediated α-1,2-fucosylation.","authors":"Wei Wen, Xiaomin Hu, Jialin Liu, Fanxin Zeng, Yihua Xu, Ye Yuan, Chunyan Gao, Xueting Sun, Bo Cheng, Jue Wang, Xinli Hu, Rui-Ping Xiao, Xing Chen, Xiuqin Zhang","doi":"10.1007/s00011-024-01932-2","DOIUrl":"10.1007/s00011-024-01932-2","url":null,"abstract":"<p><strong>Objective: </strong>Intestinal mucositis is one of the common side effects of anti-cancer chemotherapy. However, the molecular mechanisms involved in mucositis development remain incompletely understood. In this study, we investigated the function of receptor-interacting protein kinase 3 (RIP3/RIPK3) in regulating doxorubicin-induced intestinal mucositis and its potential mechanisms.</p><p><strong>Methods: </strong>Intestinal mucositis animal models were induced in mice for in vivo studies. Rat intestinal cell line IEC-6 was used for in vitro studies. RNA‑seq was used to explore the transcriptomic changes in doxorubicin-induced intestinal mucositis. Intact glycopeptide characterization using mass spectrometry was applied to identify α-1,2-fucosylated proteins associated with mucositis.</p><p><strong>Results: </strong>Doxorubicin treatment increased RIP3 expression in the intestine and caused severe intestinal mucositis in the mice, depletion of RIP3 abolished doxorubicin-induced intestinal mucositis. RIP3-mediated doxorubicin-induced mucositis did not depend on mixed lineage kinase domain-like (MLKL) but on α-1,2-fucosyltransferase 2 (FUT2)-catalyzed α-1,2-fucosylation on inflammation-related proteins. Deficiency of MLKL did not affect intestinal mucositis, whereas inhibition of α-1,2-fucosylation by 2-deoxy-D-galactose (2dGal) profoundly attenuated doxorubicin-induced inflammation and mucositis.</p><p><strong>Conclusions: </strong>RIP3-FUT2 pathway is a central node in doxorubicin-induced intestinal mucositis. Targeting intestinal RIP3 and/or FUT2-mediated α-1,2-fucosylation may provide potential targets for preventing chemotherapy-induced intestinal mucositis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1781-1801"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046590","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":"Minocycline alleviates microglia ferroptosis by inhibiting HO-1 during cerebral ischemia-reperfusion injury.","authors":"Lin Wang, Yao Wang, Mengyue Wu, Xing Jin, Yifei Chen, Zhenhuan Guo, Xiaowen Meng, Jianyou Zhang, Fuhai Ji","doi":"10.1007/s00011-024-01927-z","DOIUrl":"10.1007/s00011-024-01927-z","url":null,"abstract":"<p><strong>Objective: </strong>Ischemic stroke is a leading cause of death and disability in individuals worldwide. Cerebral ischemia-reperfusion injury (CIRI) typically results in severe secondary injury and complications following reperfusion therapy. Microglia play critical roles in the inflammatory reaction of CIRI. However, less attention has been given to microglial death in this process. Our study aims to explore microglial death in CIRI and the effects and mechanism of minocycline treatment on microglia.</p><p><strong>Methods: </strong>A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0 h, 24 h and 48 h post-operation, rats were intraperitoneally injected with 45 mg/kg minocycline. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, assessment of activated microglia and examination of mitochondrial structure were conducted and checked at 72 h after reperfusion. Additionally, an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) model was established. BV-2 cells were treated with various pharmacological inhibitors of cell death or minocycline. Cell viability, lipid peroxidation, mitochondrial structure and function, and labile Fe²⁺ and ferroptosis-associated gene/protein levels were measured. Hemin was used for further validation after transcriptome analysis.</p><p><strong>Results: </strong>In the MCAO and OGD/R models, ferroptosis was identified as a major form of microglial death. Minocycline inhibited microglia ferroptosis by reducing HO-1 expression. In addition, minocycline improved mitochondrial membrane potential, mitochondrial structures and microglial survival in vivo. Minocycline also decreased labile Fe²⁺ levels, lipid peroxidation, and expression of ferritin heavy chain (FTH) and it improved mitochondrial structure and function in vitro. Upregulation of HO-1 counteracted the protective effect of minocycline.</p><p><strong>Conclusion: </strong>Ferroptosis is a major form of microglial death in CIRI. The protective mechanism of minocycline in CIRI partially hinges on its ability to effectively ameliorate microglia ferroptosis by downregulating HO-1 expression. Consequently, targeting microglia ferroptosis is a promising treatment for CIRI.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1727-1745"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis: a potential target for acute lung injury.","authors":"Yuqi Wen, Yang Liu, Weihong Liu, Wenli Liu, Jinyan Dong, Qingkuo Liu, Zhen Yu, Hongsheng Ren, Hao Hao","doi":"10.1007/s00011-024-01919-z","DOIUrl":"10.1007/s00011-024-01919-z","url":null,"abstract":"<p><p>Acute lung injury (ALI) is caused by a variety of intrapulmonary and extrapulmonary factors and is associated with high morbidity and mortality. Oxidative stress is an important part of the pathological mechanism of ALI. Ferroptosis is a mode of programmed cell death distinguished from others and characterized by iron-dependent lipid peroxidation. This article reviews the metabolic regulation of ferroptosis, its role in the pathogenesis of ALI, and the use of ferroptosis as a therapeutic target regarding the pharmacological treatment of ALI.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1615-1629"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995666","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":"Sigma-1 receptor targeting inhibits connexin 43 based intercellular communication in chronic neuropathic pain.","authors":"Simona Denaro, Simona D'Aprile, Filippo Torrisi, Agata Zappalà, Agostino Marrazzo, Mahmoud Al-Khrasani, Lorella Pasquinucci, Nunzio Vicario, Rosalba Parenti, Carmela Parenti","doi":"10.1007/s00011-024-01926-0","DOIUrl":"10.1007/s00011-024-01926-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Neuropathic pain is a chronic condition characterized by aberrant signaling within the somatosensory system, affecting millions of people worldwide with limited treatment options. Herein, we aim at investigating the potential of a sigma-1 receptor (σ1R) antagonist in managing neuropathic pain.</p><p><strong>Methods: </strong>A Chronic Constriction Injury (CCI) model was used to induce neuropathic pain. The potential of (+)-MR200 was evaluated following daily subcutaneous injections of the compound. Its mechanism of action was confirmed by administration of a well-known σ1R agonist, PRE084.</p><p><strong>Results: </strong>(+)-MR200 demonstrated efficacy in protecting neurons from damage and alleviating pain hypersensitivity in CCI model. Our results suggest that (+)-MR200 reduced the activation of astrocytes and microglia, cells known to contribute to the neuroinflammatory process, suggesting that (+)-MR200 may not only address pain symptoms but also tackle the underlying cellular mechanism involved. Furthermore, (+)-MR200 treatment normalized levels of the gap junction (GJ)-forming protein connexin 43 (Cx43), suggesting a reduction in harmful intercellular communication that could fuel the chronicity of pain.</p><p><strong>Conclusions: </strong>This approach could offer a neuroprotective strategy for managing neuropathic pain, addressing both pain symptoms and cellular processes driving the condition. Understanding the dynamics of σ1R expression and function in neuropathic pain is crucial for clinical intervention.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1711-1726"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological targeting of adaptor proteins in chronic inflammation.","authors":"Shubhi Raizada, Alexander G Obukhov, Shreya Bharti, Khandu Wadhonkar, Mirza S Baig","doi":"10.1007/s00011-024-01921-5","DOIUrl":"10.1007/s00011-024-01921-5","url":null,"abstract":"<p><strong>Background: </strong>Inflammation, a biological response of the immune system, can be triggered by various factors such as pathogens, damaged cells, and toxic compounds. These factors can lead to chronic inflammatory responses, potentially causing tissue damage or disease. Both infectious and non-infectious agents, as well as cell damage, activate inflammatory cells and trigger common inflammatory signalling pathways, including NF-κB, MAPK, and JAK-STAT pathways. These pathways are activated through adaptor proteins, which possess distinct protein binding domains that connect corresponding interacting molecules to facilitate downstream signalling. Adaptor molecules have gained widespread attention in recent years due to their key role in chronic inflammatory diseases.</p><p><strong>Methods: </strong>In this review, we explore potential pharmacological agents that can be used to target adaptor molecules in chronic inflammatory responses. A comprehensive analysis of published studies was performed to obtain information on pharmacological agents.</p><p><strong>Conclusion: </strong>This review highlights the therapeutic strategies involving small molecule inhibitors, antisense oligonucleotide therapy, and traditional medicinal compounds that have been found to inhibit the inflammatory response and pro-inflammatory cytokine production. These strategies primarily block the protein-protein interactions in the inflammatory signaling cascade. Nevertheless, extensive preclinical studies and risk assessment methodologies are necessary to ensure their safety.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":" ","pages":"1645-1656"},"PeriodicalIF":4.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758492","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}