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1.
Luiza Marek-Jozefowicz Rafa Czajkowski Alina Borkowska Bogusaw Nedoszytko Micha A. mijewski Wiesaw J. Cubaa Andrzej T. Slominski 《International journal of molecular sciences》2022,23(2)
Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches. 相似文献
2.
Jingjuan Zhang Maoyun She Rongchang Yang Yanjie Jiang Yebo Qin Shengnan Zhai Sadegh Balotf Yun Zhao Masood Anwar Zaid Alhabbar Angla Juhsz Jiansheng Chen Hang Liu Qier Liu Ting Zheng Fan Yang Junkang Rong Kefei Chen Meiqin Lu Shahidul Islam Wujun Ma 《International journal of molecular sciences》2021,22(21)
In the present study, four large-scale field trials using two doubled haploid wheat populations were conducted in different environments for two years. Grain protein content (GPC) and 21 other yield-related traits were investigated. A total of 227 QTL were mapped on 18 chromosomes, which formed 35 QTL clusters. The potential candidate genes underlying the QTL clusters were suggested. Furthermore, adding to the significant correlations between yield and its related traits, correlation variations were clearly shown within the QTL clusters. The QTL clusters with consistently positive correlations were suggested to be directly utilized in wheat breeding, including 1B.2, 2A.2, 2B (4.9–16.5 Mb), 2B.3, 3B (68.9–214.5 Mb), 4A.2, 4B.2, 4D, 5A.1, 5A.2, 5B.1, and 5D. The QTL clusters with negative alignments between traits may also have potential value for yield or GPC improvement in specific environments, including 1A.1, 2B.1, 1B.3, 5A.3, 5B.2 (612.1–613.6 Mb), 7A.1, 7A.2, 7B.1, and 7B.2. One GPC QTL (5B.2: 671.3–672.9 Mb) contributed by cultivar Spitfire was positively associated with nitrogen use efficiency or grain protein yield and is highly recommended for breeding use. Another GPC QTL without negatively pleiotropic effects on 2A (50.0–56.3 Mb), 2D, 4D, and 6B is suggested for quality wheat breeding. 相似文献
3.
Tama Dinur Peter Bauer Christian Beetz Guido Kramp Claudia Cozma Marius-Ionu Iuracu Michal Becker-Cohen Majdolen Istaiti Arndt Rolfs Ari Zimran Shoshana Revel-Vilk 《International journal of molecular sciences》2022,23(3)
For years, the gold standard for diagnosing Gaucher disease (GD) has been detecting reduced β-glucocerebrosidase (GCase) activity in peripheral blood cells combined with GBA1 mutation analysis. The use of dried blood spot (DBS) specimens offers many advantages, including easy collection, the need for a small amount of blood, and simpler transportation. However, DBS has limitations for measuring GCase activity. In this paper, we recount our cross-sectional study and publish seven years of experience using DBS samples and levels of the deacylated form of glucocerebroside, glucosylsphingosine (lyso-Gb1), for GD diagnosis. Of 444 screened subjects, 99 (22.3%) were diagnosed with GD at a median (range) age of 21 (1–78) years. Lyso-Gb levels for genetically confirmed GD patients vs. subjects negative to GD diagnosis were 252 (9–1340) ng/mL and 5.4 (1.5–16) ng/mL, respectively. Patients diagnosed with GD1 and mild GBA1 variants had lower median (range) lyso-Gb1, 194 (9–1050), compared to GD1 and severe GBA1 variants, 447 (38–1340) ng/mL, and neuronopathic GD, 325 (116–1270) ng/mL (p = 0.001). Subjects with heterozygous GBA1 variants (carrier) had higher lyso-Gb1 levels, 5.8 (2.5–15.3) ng/mL, compared to wild-type GBA1, 4.9 (1.5–16), ng/mL (p = 0.001). Lyso-Gb1 levels, median (range), were 5 (2.7–10.7) in heterozygous GBA1 carriers with Parkinson’s disease (PD), similar to lyso-Gb1 levels in subjects without PD. We call for a paradigm change for the diagnosis of GD based on lyso-Gb1 measurements and confirmatory GBA1 mutation analyses in DBS. Lyso-Gb1 levels could not be used to differentiate between heterozygous GBA1 carriers and wild type. 相似文献
4.
Wenqing Li Dongsheng Yu Shuo Gao Jiacheng Lin Zhuoyu Chen Wei Zhao 《International journal of molecular sciences》2014,15(6):10766-10779
Candida albicans is strongly associated with severe early childhood caries (S-ECC). However, the roles of secreted aspartyl proteinases (Saps), an important virulence factor of C. albicans, in the progress of S-ECC are not clear. In our study, the Saps activities were evaluated by the yeast nitrogen base–bovine serum albumi (YNB–BSA) agar plate method and by the MTT method with bovine serum albumin (BSA) as the substrate. Genotypes of C. albicans and gene expression of Sap1–5 were evaluated. The relationships of Saps activities and genotypes with S-ECC were analyzed. The results showed that enzyme activities of Saps in the S-ECC group were significantly higher than those in the caries free (CF) group (p < 0.05). Genotypes A, B and C were detected in the S-ECC group, and genotypes A and C were detected in the CF group. In the genotype A group, Saps activity in the S-ECC group was significantly different from that in the CF group (p < 0.05). The gene expression level of Sap1 in the S-ECC group was significantly higher than that in the CF group (p = 0.001), while Sap4 expression was significantly lower than that in the CF group (p = 0.029). It can be concluded that Sap1–5 are the predominant proteinase genes expressed in C. albicans from dental biofilm and Sap1 may play an important role in the development of S-ECC. 相似文献
5.
Maria Vittoria Barone Riccardo Troncone Salvatore Auricchio 《International journal of molecular sciences》2014,15(11):20518-20537
Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptide 31–43, P31–43) is the cytokine interleukin-15 (IL-15). The role of epithelial growth factor (EGF) as a mediator of enterocyte proliferation and the innate immune response has been described. In this paper, we review the most recent literature on the mechanisms responsible for triggering the up-regulation of these mediators in CD by gliadin peptides. We will discuss the role of P31–43 in enterocyte proliferation, structural changes and the innate immune response in CD mucosa in cooperation with EGF and IL-15, and the mechanism of up-regulation of these mediators related to vesicular trafficking. We will also review the literature that focuses on constitutive alterations of the structure, signalling/proliferation and stress/innate immunity pathways of CD cells. Finally, we will discuss how these pathways can be triggered by gliadin peptide P31–43 in controls, mimicking the celiac cellular phenotype. 相似文献
6.
7.
Yongchun Shen Shujin Guo Ting Yang Liuqun Jia Lei Chen Jing An Tao Wang Fuqiang Wen 《International journal of molecular sciences》2013,14(6):11392-11401
The -173 G/C polymorphism in the macrophage migration inhibitory factor (MIF) gene has been implicated in susceptibility to inflammatory bowel disease (IBD), but the results are inconclusive. The present meta-analysis aimed to investigate the overall association between the -173 G/C polymorphism and IBD risk. We searched in Pubmed, and Embase for studies evaluating the association between the -173G/C gene polymorphism and IBD risk. Data were extracted and statistical analysis was performed using Revman 5.1 and STATA 12.0 software. A total of seven publications involving 4729 subjects (2282 IBD cases and 2447 controls) were included in this meta-analysis. Combined analysis revealed a clear association between this polymorphism and IBD susceptibility (OR = 1.48, 95% CI: 1.10–2.00, p = 0.009 for CC vs. CG + GG). Subgroup analysis by ethnicity showed that the IBD risk associated with the -173G/C gene polymorphism was significantly elevated among Asians (OR = 1.79, 95% CI: 1.08–2.96, p = 0.02), but not among Caucasians. Subgroup analysis by disease suggested that the -173G/C gene polymorphism is a risk factor for ulcerative colitis (OR = 1.62, 95% CI: 1.10–2.37, p = 0.01), but that it was not associated with Crohn’s disease. This meta-analysis suggests that the -173 G/C polymorphism in the macrophage MIF gene contributes to IBD susceptibility, specifically in Asian populations. Further studies are needed to validate these findings. 相似文献
8.
9.
Paola Galozzi Ola Negm Sara Bindoli Patrick Tighe Paolo Sfriso Leonardo Punzi 《International journal of molecular sciences》2022,23(3)
Autoinflammatory diseases (AIDs) are disorders characterised by recurrent inflammatory episodes in charge of different organs with no apparent involvement of autoantibodies or antigen-specific T lymphocytes. Few common clinical features have been identified among all monogenic AIDs (mAIDs), while the search for a common molecular pattern is still ongoing. The aim of this study was to increase knowledge on the inflammatory pathways in the development of mAIDs in order to identify possible predictive or diagnostic biomarkers for each disease and to develop future preventive and therapeutic strategies. Using protein array-based systems, we evaluated two signalling pathways known to be involved in inflammation and a wide range of inflammatory mediators (pro-inflammatory cytokines and chemokines) in a cohort of 23 patients affected by different mAIDs, as FMF, TRAPS, MKD, Blau syndrome (BS), and NLRP12D. Overall, we observed upregulation of multiple signalling pathway intermediates at protein levels in mAIDs patients’ PBMCs, compared with healthy controls, with significant differences also between patients. FMF, TRAPS, and BS presented also peculiar activations of inflammatory pathways that can distinguish them. MAPK pathway activation, however, seems to be a common feature. The serum level of cytokines and chemokines produced clear differences between patients with distinct diseases, which can help distinguish each autoinflammatory disease. The FMF cytokine production profile appears broader than that of TRAPS, which, in turn, has higher cytokine levels than BS. Our findings suggest an ongoing subclinical inflammation related to the abnormal and constitutive signalling pathways and define an elevated inflammatory cytokine signature. Moreover, the upregulation of Th17-related cytokines emphasises the important role for Th17 and/or Th17-like cells also in monogenic AIDs. 相似文献
10.
Hae Jeong Park Su Kang Kim Won Sub Kang Jin Kyung Park Young Jong Kim Min Nam Jong Woo Kim Joo-Ho Chung 《International journal of molecular sciences》2016,17(8)
The insulin-like growth factor (IGF) pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD) patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2) were genotyped using direct sequencing in 180 male ASD patients and 147 male control subjects. A significant association between rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.46–0.95) and dominant models (p = 0.013, OR = 0.57, 95% CI = 0.37–0.89). Allele frequency analysis also showed an association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46–0.94). These results suggest that IRS1 may contribute to the susceptibility of ASD in Korean males. 相似文献
11.
Li-En Hsieh Jaeyoon Song Alba Grifoni Chisato Shimizu Adriana H. Tremoulet Kirsten B. Dummer Jane C. Burns Alessandro Sette Alessandra Franco 《International journal of molecular sciences》2022,23(13)
We studied SARS-CoV-2-specific T cell responses in 22 subacute MIS-C children enrolled in 2021 and 2022 using peptide pools derived from SARS-CoV-2 spike or nonspike proteins. CD4+ and CD8+ SARS-CoV-2-specific T cells were detected in 5 subjects, CD4+ T helper (Th) responses alone were detected in 12 subjects, and CD8+ cytotoxic T cell (CTL) responses alone were documented in 1 subject. Notably, a sizeable subpopulation of CD4− CD8− double-negative (DN) T cells out of total CD3+ T cells was observed in MIS-C (median: 14.5%; IQR 8.65–25.3) and recognized SARS-CoV-2 peptides. T cells bearing the Vβ21.3 T cell receptor (TcRs), previously reported as pathogenic in the context of MIS-C, were detected in high frequencies, namely, in 2.8% and 3.9% of the CD4+ and CD8+ T cells, respectively. However, Vβ21.3 CD8+ T cells that responded to SARS-CoV-2 peptides were detected in only a single subject, suggesting recognition of nonviral antigens in the majority of subjects. Subjects studied 6–14 months after MIS-C showed T cell epitope spreading, meaning the activation of T cells that recognize more SARS-CoV-2 peptides following the initial expansion of T cells that see immunodominant epitopes. For example, subjects that did not recognize nonspike proteins in the subacute phase of MIS-C showed good Th response to nonspike peptides, and/or CD8+ T cell responses not appreciable before arose over time and could be detected in the 6–14 months’ follow-up. The magnitude of the Th and CTL responses also increased over time. In summary, patients with MIS-C associated with acute lymphopenia, a classical feature of MIS-C, showed a physiological response to the virus with a prominent role for virus-specific DN T cells. 相似文献
12.
Maria A. Ortiz F. Javier Piedrafita Adel Nefzi 《International journal of molecular sciences》2022,23(8)
A growing body of evidence suggests a pathogenic role for pro-inflammatory T helper 17 cells (Th17) in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type I diabetes, and psoriasis—diseases for which no curative treatment is currently available. The nuclear retinoic acid receptor–related orphan receptors alpha and gamma (RORα/γ), in particular the truncated isoform RORγt that is specifically expressed in the thymus, play a critical role in the activation of a pro-inflammatory Th17 response, and RORγ inverse agonists have shown promise as negative regulators of Th17 for the treatment of autoimmune diseases. Our study underscores the screening of a large combinatorial library of 1,5-disubstituted acylated 2-amino-4,5-dihydroimidazoles using a demonstrated synthetic and screening approach and the utility of the positional scanning libraries strategy for the rapid identification of a novel class of ROR inhibitors. We identified compound 1295-273 with the highest activity against RORγ (3.3 µM IC50) in this series, and almost a two-fold selectivity towards this receptor isoform, with 5.3 and 5.8 µM IC50 against RORα and RORβ cells, respectively. 相似文献
13.
Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus
Ornella Bosco Barbara Vizio Gabriella Gruden Martina Schiavello Bartolomeo Lorenzati Paolo Cavallo-Perin Isabella Russo Giuseppe Montrucchio Enrico Lupia 《International journal of molecular sciences》2021,22(13)
Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet–leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet–monocyte and platelet–granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet–leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet–leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk. 相似文献
14.
Xia Zhao Xiaosu Huang Chao Yang Yizhou Jiang Wenshu Zhou Wenhua Zheng 《International journal of molecular sciences》2022,23(11)
The abnormal immune response is an early change in the pathogenesis of Alzheimer’s disease (AD). Microglial activation is a crucial regulator of the immune response, which contributes to progressive neuronal injury by releasing neurotoxic products. Therefore, finding effective drugs to regulate microglial homeostasis and neuroinflammation has become a new AD treatment strategy. Artemisinin has potent anti-inflammatory and immune activities. However, it is unclear whether Artemisinin contributes to the regulation of microglial activation, thereby improving AD pathology. This study found that Artemisinin significantly reduced amyloid beta-peptide 1–42 (Aβ1–42)-induced increases in nitric oxide and reactive oxygen species and inflammatory factors in BV2 cells. In addition, Artemisinin inhibited the migration of microglia and prevented the expansion of the inflammatory cascade. The mechanical studies showed Artemisinin inhibited neuroinflammation and exerted neuroprotective effects by regulating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway. Similar results were obtained in AD model mice, in which Artemisinin administration attenuated Aβ1–42-induced neuroinflammation and neuronal injury, reversing spatial learning and memory deficits. The anti-inflammatory effect of Artemisinin is also accompanied by the activation of the TLR4/NF-κB signaling pathway in the animal model. Our results indicate that Artemisinin attenuated Aβ1–42-induced neuroinflammation and neuronal injury by stimulating the TLR4/NF-κB signaling pathway. These findings suggest that Artemisinin is a potential therapeutic agent for AD. 相似文献
15.
Emanuele D’Amico Carmela Leone Francesco Patti 《International journal of molecular sciences》2016,17(2)
Objectives: data on pregnancy long-term effects on multiple sclerosis (MS) course are still controversial; whether experiencing more than one pregnancy exposes one to risk of the disability‘s accrual is still unknown. We investigated differences existing in terms of disability progression among women with MS (wwMS) who had one or more children after their MS onset. Methods: Monoparous and multiparous wwMS were enrolled from the Catania MS Center, Italy, in a monocenter retrospective study. A Cox proportional hazards model was used to examine the effect of the number of parities on time from MS disease onset to EDSS 4.0 and 6.0. The study protocol was approved by the local Ethical Committee. Results: during the seven years of observation, 32.1% and 23.2% of the monoparous group reached expanded disability disease status (EDSS) 4.0 and 6.0 respectively, compared to 13.3% and 3.3% of the multiparous group (p = 0.057 and p = 0.017; respectively). The Kaplan–Meier curve analysis showed no statistically-significant differences between the two groups in reaching the two milestones. The multiparous group showed a longer time to reach the EDSS 4.0 (3.5 vs. 2.6 years, log-rank 0.57, p = 0.45). The Cox regression analysis showed that the EDSS at the time of first pregnancy (Exp(B) 9.4, CI 4.5–19.7, p < 0.001) and the time from MS onset to first pregnancy (Exp(B) 0.96, CI = 0.93–0.98, p < 0.05) were significant predictors of reaching the EDSS 4.0, whereas a model including only the EDSS one year after the first pregnancy significantly predicted (Exp(B) value of 6.4, CI 2.6–15.4, p < 0.001) the reaching of EDSS 6.0. Conclusions: Our results suggest that experiencing more than one pregnancy could not convey a different clinical outcome in wwMS. Further research is needed to confirm our results. 相似文献
16.
Marijana Vi
i Marija Katelan Ines Brajac Vlatka Sotoek Larisa Prpi Massari 《International journal of molecular sciences》2021,22(21)
Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most common inflammatory skin disease, affecting an average of 2–4% of the world’s population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients’ social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease. 相似文献
17.
Seigo Nagashima Anderson Azevedo Dutra Mayara Pezzini Arantes Rafaela Chiuco Zeni Carolline Konzen Klein Flvia Centenaro de Oliveira Giulia Werner Piper Isadora Drews Brenny Marcos Roberto Curcio Pereira Rebecca Benicio Stocco Ana Paula Camargo Martins Eduardo Morais de Castro Caroline Busatta Vaz de Paula Andra Novaes Moreno Amaral Cleber Machado-Souza Cristina Pellegrino Baena Lucia Noronha 《International journal of molecular sciences》2022,23(3)
Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE+ MCs, tryptase+ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient. 相似文献
18.
Wei-Xing Shen Jia-Hui Chen Jian-Hua Lu Yu-Ping Peng Yi-Hua Qiu 《International journal of molecular sciences》2014,15(12):22092-22108
Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, is a key regulator of the brain’s responses to injury and inflammation. Alzheimer’s disease (AD), the most common neurodegenerative disorder, involves inflammatory processes in the brain in addition to the hallmarks, amyloid-β (Aβ) plaques and neurofibrillary tangles. Recently, we have shown that T-helper (Th) 17 cells, a subpopulation of CD4+ T-cells with high proinflammation, also participate in the brain inflammatory process of AD. However, it is poorly known whether TGF-β1 ameliorates the lymphocyte-mediated neuroinflammation and, thereby, alleviates neurodegeneration in AD. Herein, we administered TGF-β1 via the intracerebroventricle (ICV) in AD model rats, by Aβ1–42 injection in both sides of the hippocampus, to show the neuroprotection of TGF-β1. The TGF-β1 administration after the Aβ1–42 injection ameliorated cognitive deficit and neuronal loss and apoptosis, reduced amyloid precursor protein (APP) expression, elevated protein phosphatase (PP)2A expression, attenuated glial activation and alleviated the imbalance of the pro-inflammatory/anti-inflammatory responses of T-lymphocytes, compared to the Aβ1–42 injection alone. These findings demonstrate that TGF-β1 provides protection against AD neurodegeneration and suggest that the TGF-β1 neuroprotection is implemented by the alleviation of glial and T-cell-mediated neuroinflammation. 相似文献
19.
Dietary Perilla Oil Inhibits Proinflammatory Cytokine Production in the Bronchoalveolar Lavage Fluid of Ovalbumin-Challenged Mice 总被引:1,自引:1,他引:1
To evaluate the anti-inflammatory effects of different dietary oils on ovalbumin-sensitized and -challenged mice. Experimental BALB/c mice were fed with different diets containing 5% corn oil [rich in linoleic acid, 18:2n-6 polyunsaturated fatty acids (PUFA), as a control diet], 5% perilla oil (rich in alpha-linolenic acid, 18:3n-3 PUFA) or 5% compound oil containing 50% corn oil and 50% perilla oil, for 5 consecutive weeks. The leukocyte count, inflammatory mediators, and cytokine levels, including proinflammatory and Th1/Th2 cytokines in the bronchoalveolar lavage fluid (BALF) from the mice were determined. The results showed that 5% compound oil administration significantly (P < 0.05) decreased eosinophilic infiltration. Dietary perilla oil could not significantly (P > 0.05) decrease the eosinophil accumulation or the secretions of inflammatory mediators such as prostaglandin E2 (PGE2), histamine, nitric oxide and eotaxin. However, dietary perilla oil significantly (P < 0.05) reduced proinflammatory cytokine (TNF-alpha, IL-1beta and IL-6) and Th1 cytokine (IFN-gamma and IL-2) production. The production of Th2 cytokine IL-10, but not IL-4 and IL-5, was also significantly inhibited by perilla oil administration. The results suggest that dietary perilla oil might alleviate inflammation via decreasing the secretion of pro-inflammatory cytokines in BALF, but failed to regulate the Th1/Th2 balance toward Th1 pole during the Th2-skewed allergic airway inflammation. 相似文献
20.
Kiera H. Harwood Rachel M. McQuade Andrew Jarnicki Elena K. Schneider-Futschik 《International journal of molecular sciences》2021,22(14)
Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) which instigates a myriad of respiratory complications including increased vulnerability to lung infections and lung inflammation. The extensive influx of pro-inflammatory cells and production of mediators into the CF lung leading to lung tissue damage and increased susceptibility to microbial infections, creates a highly inflammatory environment. The CF inflammation is particularly driven by neutrophil infiltration, through the IL-23/17 pathway, and function, through NE, NETosis, and NLRP3-inflammasome formation. Better understanding of these pathways may uncover untapped therapeutic targets, potentially reducing disease burden experienced by CF patients. This review outlines the dysregulated lung inflammatory response in CF, explores the current understanding of CFTR modulators on lung inflammation, and provides context for their potential use as therapeutics for CF. Finally, we discuss the determinants that need to be taken into consideration to understand the exaggerated inflammatory response in the CF lung. 相似文献